When did the mammalian outer ear evolve?

When did the mammalian outer ear evolve?

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All Eutheria and Metatheria have outer ears, and as far as I found out, monotremes once also had them, so they seem to be universal for mammals. Did other synapsids have them, too?

I know that soft tissue doesn't fossilize well, but isn't there any other way to find out, like muscle attachment? Has it something to do with mammalian ear bones?

Yes, it is believed to be linked to the mammalian inner ear bones. Since they act as amplifiers, the faint sounds gathered by the outer ear have a greater benefit. But really early mammals show many adaptations that they were relying very little on sight and a great deal on hearing. External ears just might not be beneficial enough unless you are really relying on hearing. The only other vertebrates that rely that much on hearing, the owls, also have external structures to help gather sound.

The fact that both developed at the same stage is circumstantial evidence that they may be linked as well.

Researchers reveal how hearing evolved

Lungfish and salamander ears are good models for different stages of ear development in these early terrestrial vertebrates. Two new studies published in the journals Proceedings of the Royal Society B and The Journal of Experimental Biology show that lungfish and salamanders can hear, despite not having an outer ear or tympanic middle ear. The study therefore indicates that the early terrestrial vertebrates were also able to hear prior to developing the tympanic middle ear. The research findings thus provide more knowledge about the development of hearing 250-350 million years ago.

The physical properties of air and tissue are very different, which means in theory that up to 99.9% of sound energy is reflected when sound waves reach animals through the air. In humans and many other terrestrial vertebrates, the ear can be divided into three sections: the outer ear, the middle ear and the inner ear. The outer ear catches sound waves and directs them into the auditory canal. In the middle ear, pressure oscillations in the air are transferred via the tympanic membrane (eardrum) and one or three small bones (ossicles) to fluid movements in the inner ear, where the conversion of sound waves to nerve signals takes place. The tympanic middle ear improves the transfer of sound energy from the surroundings to the sensory cells in the inner ear by up to 1,000 times, and is therefore very important for hearing in terrestrial vertebrates. This is reflected in the fact that different configurations are found in the vast majority of present-day terrestrial mammals, birds, reptiles and amphibians. However, available palaeontological data indicate that the tympanic middle ear most likely evolved in the Triassic period, approximately 100 million years after the transition of the vertebrates from an aquatic to a terrestrial habitat during the Early Carboniferous. The vertebrates could therefore have been deaf for the first 100 million years on land.

It is obviously not possible to study the hearing of the early terrestrial vertebrates, which became extinct long ago. However, by studying the hearing of present-day vertebrates with a comparable ear structure, it is possible to learn about the hearing of the early terrestrial vertebrates and the development of aerial hearing. A team of Danish researchers from Aarhus University, Aarhus University Hospital and the University of Southern Denmark therefore studied the hearing of lungfish and salamanders, which have an ear structure that is comparable to that of different kinds of early terrestrial vertebrates.

They studied the hearing of lungfish and salamanders by measuring auditory nerve signals and neural signals in the brainstem as a function of sound stimulation at different frequencies and at different levels. Surprisingly, the measurements showed that not only the terrestrial adult salamanders, but also the fully aquatic juvenile salamanders -- and even the lungfish, which are completely maladapted to aerial hearing -- were able to detect airborne sound despite not having a tympanic middle ear. By studying the animals' sense of vibration, the researchers were able to demonstrate that both lungfish and salamanders detect sound by sensing the vibrations induced by sound waves.

The results show that even vertebrates without outer and middle ears are capable of detecting airborne sound. This means that adaptation to aerial hearing following the transition from aquatic to terrestrial lifestyles during the Early Carboniferous was presumably a gradual process, and that the early terrestrial vertebrates without tympanic middle ears were not deaf to airborne sound during the first 100 million years on land. In addition to making us wiser about hearing in general, the results can provide inspiration in the future to developing clinical treatments for hearing loss.

Mystery Of Mammalian Ears Solved

A 30-year scientific debate over how specialized cells in the inner ear amplify sound in mammals appears to have been settled more in favor of bouncing cell bodies rather than vibrating, hair-like cilia, according to investigators at St. Jude Children's Research Hospital.

The finding could explain why dogs, cats, humans and other mammals have such sensitive hearing and the ability to discriminate among frequencies. The work also highlights the importance of basic hearing research in studies into the causes of deafness.

"Our discovery helps explain the mechanics of hearing and what might be going wrong in some forms of deafness," said Jian Zuo, Ph.D., the paper's senior author and associate member of the St. Jude Department of Developmental Neurobiology. "There are a variety of causes for hearing loss, including side effects of chemotherapy for cancer. One strength of St. Jude is that researchers have the ability to ask some very basic questions about how the body works, and then use those answers to solve medical problems in the future."

The long-standing argument centers around outer hair cells, which are rod-shaped cells that respond to sound waves. Located in the fluid-filled part of the inner ear called the cochlea, these outer hair cells sport tufts of hair-like cilia that project into the fluid. The presence of outer hair cells makes mammalian hearing more than 100 times better than it would be if the cells were absent.

As sound waves race into the inner ear at hundreds of miles per hour, their energy--although dissipated by the cochlear fluid--generates waves in the fluid, somewhat like the tiny waves made by a pebble thrown into a pond. This energy causes the hair cell cilia in both mammals and non-mammals to swing back and forth quickly in a steady rhythm.

In mammals, the rod-shaped body of the outer hair cell contracts and then vibrates in response to the sound waves, amplifying the sound. In a previous study, Zuo and his colleagues showed that a protein called prestin is the motor in mammalian outer hair cells triggers this contraction. And that is where the debate begins.

While both mammals and non-mammals have cilia on their outer hair cells, only mammalian outer hair cells have prestin, which drives this cellular contraction, or somatic motility. The contraction pulls the tufts of cilia downward, which maximizes the force of their vibration. In mammals, both the cilia and the cell itself vibrate. Thus far the question has been whether the cilia are the main engine of sound amplification in both mammals and non-mammals.

One group of scientists believes that somatic motility in mammalian outer hair cells is simply a way to change the height of the cilia in the fluid to maximize the force with which the cilia oscillate. That, in turn, would amplify the sound. An opposing group of scientists maintains that although the vibration of the outer hair cell body itself--somatic motility--does maximize the vibration of the cilia, the cell body works independently of its cilia. That is, vibration of the mammalian cell dominates the work of amplifying sound in mammals.

"If somatic motility is the dominant force for amplifying sound in mammals, this would mean that prestin is the reason mammals amplify sound so efficiently," Zuo said.

In the current study, Zuo and his team conducted a complex series of studies that showed in mammals that the role of somatic mobility driven by prestin is not simply to modify the response of the outer hair cells' cilia to incoming sound waves in the cochlea fluid. Instead, somatic motility itself appears to dominate the amplification process in the mammalian cochlea, while the cilia dominate amplification in non-mammals.

Zuo's team took advantage of a previously discovered mutated form of prestin that does not make the outer hair cells contract in response to incoming sound waves as normal prestin does. Instead, the mutated form of prestin makes the cell extend itself when it vibrates.

The St. Jude researchers reasoned that if altering the position of the cilia in the fluid changes the ability of the cilia to amplify sound, then hearing should be affected when the mutant prestin made the cell extend itself. Therefore, the team developed a line of genetically modified mice that carried only mutant prestin in their outer hair cells. The researchers then tested the animals' responses to sound.

Results of the studies showed no alteration in hearing, which suggested that it did not matter whether the outer hair cells contracted or extended itself, that is, raised or lowered the cilia. There was no effect on amplification. The researchers concluded that somatic motility was not simply a way to make cilia do their job better rather, there is no connection between the hair cell contractions and how the cilia do their job. Instead, somatic motility, generated by prestin, is the key to the superior hearing of mammals.

A report on this work appears in the advanced online issue of "Proceedings of the National Academy of Science."

Other authors of this study include Jiangang Gao, Xudong Wu and Manish Patel (St. Jude) Xiang Wang, Shuping Jia and David He (Creighton University, Omaha, Neb.) Sal Aguinaga, Kristin Huynh, Keiji Matsuda, Jing Zheng, MaryAnn Cheatham and Peter Dallos (Northwestern University, Evanston, Ill.).

This work was supported in part by ALSAC, The Hugh Knowles Center and the National Institutes of Health.

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Materials provided by St. Jude Children's Research Hospital. Note: Content may be edited for style and length.

Human ear

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Human ear, organ of hearing and equilibrium that detects and analyzes sound by transduction (or the conversion of sound waves into electrochemical impulses) and maintains the sense of balance (equilibrium).

The human ear, like that of other mammals, contains sense organs that serve two quite different functions: that of hearing and that of postural equilibrium and coordination of head and eye movements. Anatomically, the ear has three distinguishable parts: the outer, middle, and inner ear. The outer ear consists of the visible portion called the auricle, or pinna, which projects from the side of the head, and the short external auditory canal, the inner end of which is closed by the tympanic membrane, commonly called the eardrum. The function of the outer ear is to collect sound waves and guide them to the tympanic membrane. The middle ear is a narrow air-filled cavity in the temporal bone. It is spanned by a chain of three tiny bones—the malleus (hammer), incus (anvil), and stapes (stirrup), collectively called the auditory ossicles. This ossicular chain conducts sound from the tympanic membrane to the inner ear, which has been known since the time of Galen (2nd century ce ) as the labyrinth. It is a complicated system of fluid-filled passages and cavities located deep within the rock-hard petrous portion of the temporal bone. The inner ear consists of two functional units: the vestibular apparatus, consisting of the vestibule and semicircular canals, which contains the sensory organs of postural equilibrium and the snail-shell-like cochlea, which contains the sensory organ of hearing. These sensory organs are highly specialized endings of the eighth cranial nerve, also called the vestibulocochlear nerve.

Mammalian middle ear evolution

Ask any school child what makes a mammal different from a non-mammal, and they might mention fur, mammary glands, live birth and warm-bloodedness. Setting aside the exceptions one would expect for a biological rule (platypus and echidnae lay eggs, birds are warm-blooded), these soft tissue features are not always useful to palaeontologists as they rarely, if ever, are preserved in fossils. If, however, you were to ask a student of mammalian evolution, they would probably also include the novel mammal jaw joint and the three-ossicle middle ear chain, which contrasts to the one bone in other amniotes such as reptiles and birds. Perhaps surprisingly the extra middle ear bones are the repurposed jaw joint bones of non-mammals. The evidence for this can be followed through a number of intermediate forms in the fossil record of Mesozoic ancestral mammals. This has become a textbook example of an evolutionary transition. Several key groups of Mesozoic mammal ancestors had both the new mammalian jaw joint and an old non-mammal joint that had a dual role in both the jaw and ear known as a partial mammalian middle ear. One of the last anatomical changes that led to the definitive mammal middle ear from the double joints of these primitive mammals was the detachment of the old jaw joint from the mandible by the loss of the Meckel’s cartilage linking the malleus to the mandible. This final step resulted in the definitive mammalian middle ear. The development of the mammal middle ear reflects the evolutionary transition, as the malleus and incus initially develop as part of the lower jaw, and separate late in development.


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We have just published an article in Nature Ecology and Evolution that exploits modern comparative developmental biology that reveals that the activity of bone- and cartilage-eating clast cells is a key mechanism by which the middle ear separates from the jaw, allowing for the evolution of the definitive mammalian middle ear.

I first gained an interest in the evolution of the mammalian jaw and ear during my PhD work when I studied the development of the mouse mandibular skeleton. Eventually my PI Abigail Tucker and I won the funding that allowed us to pursue our investigations into the ear and jaw from an evo-devo perspective. Shortly after our work began, we discovered that Karen Sears and her then PhD student Dan Urban in Urbana, Illinois were also taking a similar approach and so rather than compete we all decided that we should collaborate. Across the two labs we studied the development of middle ear and jaw in mice, opossum and various reptile species. Good fortune meant that Zhe-Xi Luo, a palaeontologist in Chicago with an expertise in mammalian evolution, could be brought on board, as he was already acting on the thesis committee for Dan’s PhD. We therefore had assembled a great team of developmental and evolutionary biologists to address this fascinating question.

In London I had been studying histological sections of Meckel’s cartilage in mice during the time that it breaks down, trying to understand how this happens. It seemed likely that clast cells, which eat up the extra cellular matrix of bone and cartilage as part of normal remodelling during development and homeostasis, played an important role.

We looked for these cells in two species of mammal, a placental (mouse) and a marsupial (opossum), and in non-mammals, corn snakes and geckos. Satisfyingly, while we could see the clast cells at work on Meckel’s cartilage during its breakdown in mice and opossums, they were not found in the cartilage of either reptile. As such we concluded that clast cells are an important player in the separation of the middle ear from the mandible.

Being developmental biologists we like to break things to see how they work, so we looked in a transgenic mouse that lacked a gene called cFos. This gene has many jobs, including acting as a key component of the clast cell differentiation process, and so cFos null mice are not able to make clast cells. Happily (for us) there was no breakdown of MC in these mice when we looked in early postnatal stages. To make sure that this wasn’t due to a general delay in development - these mice are pretty small - we nursed some animals to adult stages. This included feeding the mice a soft diet since the lack of clast cells means that the teeth were unable to erupt from within the mandible bone. Amazingly, when we looked in adult cFos null mice, we found that not only did the Meckel’s cartilage stick around, but it appeared to have ossified. This implied that the branches of the primitive mammals that gave rise to modern mammals included those animals that had an ossified cartilage.

Meanwhile, Karen and her team in Illinois were able to replicate these findings by treating opossum pups with an osteoporosis-treating drug that inhibits clast cell activity. We could therefore prove that this mechanism is conserved throughout therian mammals. Finally Luo helped us to carefully compare our mutant mice with the fossil record. In doing so we were able to show that not only did the mutants resemble the fossils in the persistence of the Meckels’s cartilage, but also in the groove the cartilage leaves on the inner surface of the mandible bone. This groove is found much more often in fossils than an ossified Meckel’s, which may be very thin and therefore easily lost.

Working together across three different institutions in two countries, our team demonstrated the power of collaborations with other disciplines and expertise. Finally, we also show that the old-school morphological and paleontological approach can be greatly informed by more modern wet-lab approaches.


Psychoacoustic and behavioral experiments 1, 2 exhibit a marked frequency dependence of the mammalian hearing sensitivity 3,4,5,6 (Fig. 1). Over more than a decade, the biophysical origins of this dependence have now remained a subject of debate 3, 7,8,9,10 , despite the great development of measurement and modeling technologies. To compare directly psychoacoustic to biophysical results - which is what is generally done and what we will do below - the auditory signal would be required to remain unaltered along the auditory pathway. This is far from obvious, but recently 11 it was shown that the auditory pathway may achieve this property by making substantial use of stochastic resonance in the auditory fibers. Here, we show that the same mesoscopic nonlinear physics model of the mammalian cochlea that has successfully reproduced other challenging hearing phenomena 12,13,14,15,16 might also provide an explanation of the observed sensitivity dependence on frequency.

Behavioral audiograms of prairie dog 52 , elephant 53 , lemur 54 , domestic cat 55 , human psychoacoustial hearing threshold 4 , white-beaked dolphin 56 (smoothened data), false killer whale 57 , from top to bottom, sorted by the curves’ minima. The full extension of the audiogram was not accessed in all cases. Reference sound pressure p 0 = 20 μPa.

Let us briefly summarize the key points of controversy underlying this debate. One viewpoint emerges from following the most straightforward way of approaching this question, by conceiving the hearing sensor as composed of a resonator (outer ear), an impedance matcher (middle ear), and a Fourier analyzer of the auditory signal (inner ear), respectively (see the references given in the corresponding discussion in ref. 3). The outer ear is commonly modeled by a semi-closed cylinder 17, 18 of about 30 mm. This leads to a resonance in the range of 3 kHz as the first, and the second one at tripled frequency effects that are indeed observed in measured data (cf. Figs 1 and 3). The modeling of the influence of the middle ear in this process is more challenging, due to the presence of additional, complicating mechanical and spatial elements (cf. refs 19,20,21). The hearing pathway overall response is then obtained by performing a summation over the corresponding individual logarithmic responses. With the development of experimental techniques, this approach could be calibrated with measured animal data. In this way, qualitative aspects of the behavioral data (Fig. 1) could be reproduced for some mammals (e.g. for human hearing 10, 22 ), whereas for a number of other mammals, the approach appears to have been unsuccessful so far 3 . A deviant viewpoint emerges from a more recent analysis by Ruggero et al. 3 , who re-evaluating middle ear transfer function data, arrived at the result that a number of animal middle ear transfer functions appear to cover a much broader interval than their actual hearing frequency interval (cf. the discussion and the corresponding Figs in ref. 3, and further refs therein). This led these authors to conclude that the inner ear could have “a crucial role in setting the frequency limits..” but that “It remains to be seen whether the finding that the bandwidth of middle-ear vibrations exceeds that of the audiogram in chinchilla, gerbil, guinea pig, horseshoe bat, pigeon, and turtle will be confirmed..” 3 . A number of subsequent biological measurements and finite element simulations seem to support the lack of frequency specificity of the outer and middle ear (e.g., refs 23, 24 and 25, respectively). For the reader’s convenience, data underlying this view are presented for the example of the Gerbil’s hearing system in our Suppl. Mat. section I. These results have, however, been challenged (cf. ref. 7 and the discussion in ref. 24) the main role in shaping hearing sensitivity seems to be commonly still attributed to the outer and middle ear.

In this dispute, regardless of which arguments will ultimately prevail, a critical analysis of the role of the active inner ear is still missing, and the analysis performed so far must thus be seen as incomplete. We contribute to the debate by investigating whether, and if so, under what conditions, an established model of the cochlea could reproduce the observed frequency dependence at all.

The biophysically detailed differential equation model of the cochlea that we use below to address this question 26 is based on a shallow fluid wave propagating along the basilar membrane (BM), described by fluid and BM mass density, depth of the cochlear fluid canal, BM stiffness and surface tension. To these passive properties, active amplification found in the cochlea is added in the form of outer hair cell dynamics described at a mesoscopic level 26 in terms of the Hopf small signal amplifier property 27,28,29,30,31 . A micro-electro-mechanical model of the embedded hair cell dynamics, that would account for the whole mammalian hearing range, is presently still missing. This, however, is not detrimental since the underlying Hopf small-signal amplifier model, which has been demonstrated to be the working principle of several animal’ hearing’ implementations (e.g., the frog’s sacculus 32,33,34 , or Drosophila’s antennas 35, 36 ), can naturally be implemented into the biophysical framework and can directly serve for implementing the biophysically observed amplification response.

Our biophysical description is of a generalist nature. It can be easily specified to implement generalist or specialist hearing properties, as well as to implement defective hearing properties (for an example, see ref. 37). Moreover, it can directly be translated into a computationally optimized form where the underlying differential equation model is discretized into a series of serially connected cochlea sections. A section, see Fig. 2, embraces the frequency-specific amplification by a patch of the basilar membrane with attached outer hair cells surrounded by the cochlear fluid. In the section, a long list of local or microscopic parameters (relevant for describing the detailed passive aspects of the cochlea or micro-electrical-mechanical of active amplification), is collapsed into two parameters per section, the Hopf bifurcation parameter μ (c.f. Suppl. Mat. II) and the section’s preferred frequency. In the human case (a hearing generalist, see below), the frequencies are preferably logarithmically spaced this implementation is fully described, e.g., in the supplement of ref. 16, see also refs 12,13,14,15,16.

Cochlea section from a Hopf cochlea composed of several serially connected sections. A complex (real and imaginary part) signal from a precedent section (indexed by j − 1) enters the following section (indexed by j). Signal components that are close to the characteristic frequency (_^<(j)>) of the Hopf amplifier j are most strongly amplified and can be read off at this point, where the maximal amplification is determined by the Hopf parameter μ (j) . Thereupon, the signal component is attenuated by a low-pass Butterworth filter, whereas sound components of lower frequencies are passed on to the next section (_^<(j+mathrm<1)>>) (see text). The nonlinear nature of the amplification leads to all kinds of phenomena known from experiments on human hearing (see our Suppl. Mat. III).

The obtained sensor has been demonstrated to reproduce all observed salient nonlinear effects of mammalian hearing, from frequency- and stimulation strength dependent amplification profiles, to the correct combination-tone generation, to the phenomena of pitch perception (pitch shift effect, loudness-dependence of pitch). Detailed comparisons of biophysical key data to the corresponding data from the Hopf cochlea, were provided in earlier publications 13, 15 , and in particular in the supplemental materials of refs 16 and 38. For convenience, a collection of salient comparisons between the biophysical data and corresponding results from our model is furnished in our Suppl. Mat. III.

Hopf amplifiers can be tuned towards higher or lower sensitivity, by adjusting their Hopf parameters closer or further away, respectively, from the Hopf bifurcation point. A species’ hearing characteristics are, at this level, characterized by a list of preferred frequencies and the sections’ “normal” sensitivities. Already in ref. 26 it was exhibited that for human-like hearing, a down-tuning of the Hopf amplifiers’ sensitivities towards more apical frequencies would be appropriate, where an analytic expression was provided. In the biological example, amplifier sensitivity can, moreover, be modulated to some extent by efferent connections. In ref. 39 (see our Suppl. Mat. II), we have shown that this property is likely a major ingredient of auditory source separation in the biological example, and how this mechanism, that turns our sensor from a “hearer” into a “listener”, can be easily implemented within the present framework. Comparative hearing research reveals for auditory specialists great frequency optimization of the BM-place-frequency map, where generalists show a much smoother variation. Both categories, however, deviate from the purely exponential dependence 40 that would be compatible with a cochlea where all Hopf parameters have the same value (a “flat-tuned” cochlea) on a logarithmic frequency spacing. The fact that animals of variable sizes (ferret, elephant) have substantial lower hearing frequency bounds compared to humans, points to tuning as an expression of evolutionary adaptation of the different species, rather than to limitations contributed by the mechano-electrical OHC and hair bundle design. Additionally, species-specific emphasized frequency intervals may be due to neural conditioning, by which efferent connections may be designed or taught to enhance or to suppress desired and undesired, respectively, frequency ranges 39 . An observed gentle decay of the endocochlear potential along the cochlear duct is observed (which can be expected to negatively affect the efficiency of the outer hair cells (e.g., ref. 41)) and changes in the micro-mechanical properties along the cochlear duct 42 seem, in this context, to be of secondary relevance. These mentioned observations, however, exhibit that in the context of non-local aspects of the cochlea, such as the hearing threshold’s frequency dependence across the hearing range, a tuning of the amplification along the cochlear duct must be considered. In a cochlea model based on Hopf amplifiers, ‘tuned’ amplification profiles could be obtained in two ways: by a changed density of OHC working at the same amplification strength (biologically, we observe a lowered OHC density towards the apex), or by the tuning of the sensitivity of the amplifiers. In the context of the mesoscopic approach followed in our modeling, a tuning of the sensitivity is the simpler solution. In the following, we used a tuning suggested by the estimate provided in ref. 26 that was shown to provide an accurate reproduction of Smoorenburg’s 43 pitch shift experiments 15 . Upon such tuning, previous observations regarding local amplification, combination tone decay, phase behavior procession along the cochlea, and sound selectivity by tuning 15 , remain valid (see our Suppl. Mat. III).

To place our model into the context of psychoacoustic hearing experiments, we start from the following: if for the cochlea a Hopf parameter around (mu simeq -0.2) is chosen and if about −114 dB input to the Hopf cochlea is taken to correspond to 0 dB SPL in biology 15 , the local amplification response curves of the Hopf cochlea reliably reproduce the behavior of the prominent biophysical examples obtained at high to central hearing frequencies at moderate sound pressure levels 41, 44 , given a “natural” discretization of the cochlea 16 . A 10 dB SPL input, which characterizes the hearing threshold for the most sensitive part of the human frequency range 15 , then corresponds to a −104 dB input to the Hopf cochlea, leading to a response of about −50 dB. It is therefore natural to define a node to be ‘activated’ if the amplified signal (of an arbitrary input signal), reaches at the node above a −50 dB threshold (the model’s hearing threshold). Other choices of the threshold within a ±10 dB bandwidth (including, in particular, the −53 dB value that has been used for the reproduction of the experimental data of combination-tone hearing experiments in ref. 15), did not affect any of the following results. For our experiments, we stimulated the Hopf cochlea by pure tone signals of frequency f, with the amplitude A set to a predefined level L in dB, i.e., A = 10 (L/20) . Pure-tone stimulations were used as they lead to essentially one activated locus (simple non-pure stimuli lead to complex activation response patterns 16, 45 that are more difficult to work with). From a range between −120 and −10 dB, stimulation levels were selected in steps of 1 dB, at stimulation frequencies from a (0.02,20) kHz interval, using logarithmic spacing. At each section, the response (R=20,>_<10>(y)) was measured, where y denotes the maximal amplitude of the response obtained during the observation time. The input level for which the maximum R max across all sections was closest to −50 dB, was taken as the hearing threshold input level.

For our main experiments, a Hopf cochlea with 31 sections, spanning 110–19912 Hz, tuned at Hopf parameters μ at −0.1 for the first few sections (coding for the highest frequencies), followed by a steady decrease of −0.0105 per section, was used (the latter value depends on the particular discretization). Also neighboring configurations were tested (e.g. where an immediate decay was implemented) all of them reproduced the experimental audiogram from ref. 4 remarkably well (c.f. Fig. 3).

Gray curves: data from Zwicker’s publication 4, 58 , dashed part indicating extrapolations. Gray shading: observed human variability. Red curve: cochlea response with biological tuning, where the inset shows the tuning of Hopf parameters used (see text). Across sensible tuning variations, the overall behavior is remarkably stable. Three boxes indicate areas along the cochlear duct where our model deviates from the biological example (see text). Dashed vertical line: frequency location of the last section of the cochlea model.

The deviations between psychoacoustic measurements and estimates and our simulation results have the following natural explanations (Fig. 3, boxes from right to left). At the highest frequencies, a precipitous rise of the hearing threshold curve at the base has been estimated by ref. 4 (first box, dashed line). Our analytic model of the passive model of the basilar membrane 26 corroborates that salient effects of the BM attachment are basal to the characteristic locus of our first amplifier (if reliable biophysical data were available, our computational approach could be adapted to take such data into account as well (cf. first box and Fig. 4)). After exploiting the full interaction range - at the given discretization and sensitivity of our Hopf cochlea, this influence extends over a range of roughly 6–8 sections (cf. Fig. 5, lower panel) - a region of optimal sensitivity is reached where the behavior predicted by our model deviates from the biological example (second box). This deviation is due to the well-known resonance effect by the outer and the middle ear, known to contribute a stimulation increase effect up to 10 dB, confined to the area of interest around 4000 Hz 18 . Taking this into account yields a very good agreement with the biological example. Further towards the apex the sensitivity slowly decreases, due to the decrease in Hopf sensitivity. Beyond the characteristic frequency of the last amplifier section, our model deviates from the example as the discretization of our model fails to account for the more gradual amplification decrease of the biological example (indicated by a reduced number of OHC-rows), third box. Beyond the characteristic frequency of the last amplifier, the amplification vanishes therefore more abruptly than in the biological example, and it is also known that towards the apex, the membrane vibrations are less sharply tuned 46 . Toward the physical end of the basilar membrane, also other salient effects are neglected, in particular the vanishing pressure difference between the scala media and the scala tympani that must be expected to have a strong effect on the biological response. We suspect that if that frequency region could be accessed experimentally (a quite difficult endeavor 47 ), a precipitous rise of the curve would be observed. Reliable data, however, are sparse also in this case.

Sensitivity at the borders of the frequency hearing interval exhibiting that the first section determines the high-frequency response. The response at the low-frequency border, however, emerges as a cumulative, collective result that will also be influenced by boundary and discretization effects. Dashed vertical lines indicate the locations of the Hopf amplifiers’ characteristic frequencies.

Mechanism underlying frequency dependence of the hearing threshold. Lower panel: evolution of the amplification profile along the cochlear duct, for seven input frequencies. Upper panel: obtained hearing threshold. For clarity of the effect, a flat-tuned cochlea of 29 sections was used. Horizontal dashed-dotted line: input amplitude.

The above interpretation can be corroborated by analytical considerations that, moreover, nicely exhibit the fundamental mechanism by which the frequency dependence of the hearing threshold is obtained in our model. The complex-number normal form Hopf equation, rescaled by a characteristic angular frequency ω ch and subjected to a sinusoidal forcing signal, (dot=_((mu +i)z-<|z|>^<2>z+F^)) , (zin >) , can be rewritten in a coordinate frame that rotates with the forcing: (dot=_(mu z-<|z|>^<2>z+F)+i(_-omega )z,) . Assuming after some transient period a 1:1 locked solution (existence verified in the numerical experiments), z(t) = ae is constant in this coordinate frame, and one can obtain a cubic polynomial in a 2 that can be solved for the real amplitude a 12, 30, 45 . Alternatively, one can separate the locking criterion into two conditions (dot=mu a-^<3>+F,cos ,varphi =0) , and (dot=(_-omega )a-_F,sin ,varphi =0) . The first condition has no direct dependence on ω, but from the second, assuming (|varphi | o frac<2>) for large |ω chω|, we can approximate

This approximation, which shows good agreement with the full analytic solution for small negative μ and small forcing F (cf. Suppl. Mat. II), provides a clear picture of the collective amplification that is responsible for the pure-tone hearing threshold curve. To focus and separate influences, we illustrate our arguments using a flat-tuned Hopf cochlea (i.e., a cochlea for which all Hopf parameters are all at the same value, μ i = const., i = 1 … 29). For input frequency (omega ll _) , we have a Hopf response amplitude aF. This defines a natural limit for the number of higher frequency Hopf cochlea sections that most significantly influence the amplification cascade of an input signal (in our setting, roughly the mentioned 6–8 sections, cf. Fig. 5). Over the frequency range covered by those high-frequency sections, the hearing threshold decreases, due to the onset of the amplification cascade. After the interaction range is exploited, the maximum hearing sensitivity is reached, and a flat hearing threshold curve is maintained until the characteristic frequency of the last section is reached. After the last cochlea section, as the input frequency moves beyond the amplification envelope of the last cochlea sections, the hearing threshold increases again. This also implies that for very low frequency, the input threshold of the Hopf cochlea approaches, in the model, the pre-specified output threshold of −50 dB (i.e., aF).

In this way, essential frequency dependence of the hearing threshold emerges from a neighborhood preceding and including the signal frequency’s best matching amplifier. This neighborhood delivers the principal part of the amplification, where the asymmetry in frequency (cf. Fig. 3, Suppl. Mat. III) is the consequence of the Butterworth filter. The obtained amplification can be modified by a tuning of the Hopf amplifiers’ sensitivity along the cochlear duct, such as is the case in human hearing, where we observe a simple continued down-regulation of the sensitivity. On the high frequency branch, amplification accelerates by recruiting ever more amplifiers of this neighborhood, until the maximal neighborhood range is reached. After this point, the slow detuning of the amplifiers’ efficiency becomes effective, until the signal frequency is below the characteristic frequency of the last amplifier. Here, a de-recruitment process sets in, where only the remaining amplifiers of the neighborhood - at non-optimal characteristic frequencies - still contribute to the amplification. As our system is based on a detailed model of the inner ears’ physical properties, we expect this explanation to hold for the biological example as well.

While the questions of how the microscopic mechano-electromotile systems co-operate to arrive at the Hopf property 47,48,49 and how this translates to the mesoscopic approach 50 are of great interest themselves, our mesoscopic cochlea model embraces both effects within its Hopf section. The model reproduces to great accuracy not only the naturally measured local nonlinearities 13, 38 and ensuing salient nonlinear phenomena of hearing (such as the perception of pitch), but also the measured psychoacoustic hearing threshold’s dependence on frequency. On this mesoscopic level, we see strong evidence for a potential essential role of the inner ear in determining the sensitivity dependence of mammalian hearing. While our model is composed of identical amplifiers (modulo their characteristic frequencies and μ-values), it is their nonlinear interaction that binds the cochlea towards having its specific, biophysically and psycho-acoustically observed frequency-specific sensitivity. This uncovered feature is, on a more global scale of the cochlea, an even more fundamental manifestation of nonlinearity in hearing, compared to the fact that for signals composed of different frequencies, combination tone avalanches emerge (cf. ref. 16). Our results also highlight a strong role of nonlinear dynamics in explaining and reproducing biological nature: in our model, the same nonlinear principle, expressed in its most simple form, reproduces without requiring any additional efforts a whole spectrum of previously unexplained salient hearing phenomena (see our Suppl. Mat. III). This has a number of advantages, in abstract modeling and also when it comes to engineering implementations. To arrive at an amplification of incoming sound at any desired level, only a change of the Hopf parameter is required, with a much reduced latency (compared to the activation of a cascade of linear amplifiers, where the amplification strength would be naturally bounded by the number of elements of the cascade). Such tuning is, in particular, fruitful for the implementation of the role of the biological efferent connections to the cochlea. These connections are likely involved in the enhancement of desired auditory objects from an auditory landscape, by the enhancement of the corresponding frequency channels 39 (although we deal with a nonlinear system). On a more general level, the approach taken here may open up new perspectives for research and engineering in the field of sensors. As one example, our analytical approximation to the full nonlinear-physics based model of the cochlea, reveals “filters” of a very particular form and enormous spatially extended overlaps. A classical engineer would hardly come up with such a design that poses a significant paradigm challenge to the conventional state of art. In the field of hearing, our modeling approach might provide insight into questions that are inaccessible to current experimental techniques, by guiding towards the formulation of closely related problem statements that can be experimentally accessed.

The question whether the outer-middle or the inner ear provides the limiting factor of the hearing, might, in our view, be wrongly posed after all. If we admitted that the inner ear is sufficient for explaining frequency sensitivity, could we conclude that the outer and middle ear have (apart from the already mentioned resonances) a minor role in shaping the hearing threshold? Obviously, evolution may occasionally have shaped ear canal and outer ear resulting in a constraint of hearing sensitivity. However, even the evolutionary adaption from today’s land-based towards water-based mammals did not substantially affect the cochlear construction principle 36, 51 , while it clearly affected the outer ear. In this light, while the inner ear should not be seen as the only relevant part, it seems that, as the evolutionarily less variable construction, it has the dominant role for shaping the hearing threshold. In either case, our results strongly suggest that the various statements in textbooks exhibiting that hearing sensitivity is generally determined by the outer and middle ear (but not by the inner ear), may be historically biased and not be fully justified.

Auditory Development and Hearing Disorders

External Ear

At 6 weeks the outer ears start developing from folds on the front neck area of the embryo. A set of six auricular hillocks or bumps arises for each ear. These hillocks are visible as early features of the adult ear. The ear canal forms at 5 weeks, and at about 12 weeks a plate forms at the inner end of the canal. This plate remains until about 7 months, when it dissolves and the remaining tissue forms the tympanic membrane or eardrum. The outer ear and ear canal continue to grow longer after birth, reaching adult sizeat about 9 years. Failure of the outer ear to develop at all is called anotia, limited growth is called microtia, while partial or complete closure of the ear canal is called atresia.

Chapter 10: Ears

1) There are three parts to the ear the inner ear, middle ear, and outer ear. The pinna, or the flap of the external ear, is a body part only found in mammals.

2) The discovery that the ear bones of mammals may have some correlation to the jaw bones of reptiles began with Karl Reichert, a German anatomist. Mammals have three bones in the middle ear, while reptiles and amphibians have only one. Thus, these bones had to come from somewhere. He observed gill arches in several species to see where they ended up within the skull, and discovered that two of the ear bones present in mammals corresponded to bones in the jaws of reptiles. He concluded that “the same gill arch that formed part of the jaw of a reptile formed ear bones in mammals” (Shubin 160). Another German anatomist, Ernst Gaupp, continued this theory, believing that the three middle ear bones showed a tie between reptiles and mammals. The two mammalian middle ear bones that correlated to reptiles, the malleus and the incus, evolved from parts of the reptilian jaw. In the 1840s, new fossil creatures were being discovered in South Africa and Russia when put together, many of them were described as mammal-like reptiles.

By 1913, embryologists and paleontologists began to work together, and with Gaupp’s theory, began to look at these fossilized skeletons. They discovered that the most reptilian of these skeletons only had a single bone in the middle ear, just like current reptiles do, and a jaw composed of many bones. However, the more mammalian of these skeletons showed the bones at the back of the reptilian jaw getting smaller until they eventually became part of the middle ear of mammals. This proved that the malleus and incus evolved from jawbones.

Similar discoveries were made between humans and sharks. The stapes is a second arch bone in the ear, and corresponds to a bone in sharks and fish known as the hyomandibula. The hyomandibula is a large rod that joins the upper jaw with the braincase. Looking at fossils being traced from sharks to Tiktaalik to amphibians, there is a clear trend of the hyomandibula shrinking in the upper jaw and eventually shifting position to play a role in hearing.

3) The Pax 2 gene is active in the ear and starts a chain reaction that allows for the inner ear to develop. If a mutation in humans or mice knows this gene out the inner ear cannot properly form. This is a major gene that is essential for proper development.

In the developing ears of opossums, echoes of evolutionary history

When we are confronted with the remarkable diversity and complexity of forms among living things—the lightweight and leathery wings of a bat, the dense networks of genes that work together to produce a functional cell—it can be hard to imagine how chance mutations and selective processes produced them. If we could rewind evolutionary time, what would we see?

In a new study published in Proceedings of the Royal Society B (DOI: 10.1098/rspb.2016.2416), animal scientists at the University of Illinois at Urbana-Champaign, King’s College London, and the University of Chicago have discovered that hidden in the development of opossums is one possible version of the evolutionary path that led from the simple ears of reptiles to the more elaborative and sensitive structures of mammals, including humans.

When mammalian middle ear bones develop, they begin as part of the arch of cartilage that makes up the embryonic jaw. In reptiles, these structures remain connected to the jaw as developmental processes gradually convert the cartilage to bone.

Three tiny bones in the middle ear of mammals form a mechanism that converts the air vibrations of sound into the electrical impulses understood by the brain. Three of these bones are known by names that describe their shapes, either in Latin or in English: the malleus (hammer), incus (anvil), and stapes (stirrup). In the simpler ears of reptiles, as well as the shared ancestors of both groups, only the stapes is found in the middle ear, while analogs of the malleus and incus form part of the jaw.

The sharp contrast between the precise structure of these tiny mammalian bones and their non-auditory reptilian counterparts drew the attention of Associate Professor of Animal Biology Karen Sears and postdoctoral researcher Daniel Urban, who led the study. Sears is a member of the Carl R. Woese Institute for Genomic Biology (IGB) Urban is an IGB Fellow.

“We came at this project through the approach of evolutionary developmental biology (evo-devo), which looks at the development of an organism . . . to help understand its evolutionary history,” said Urban, explaining their experimental approach. An exciting aspect of the project for him was that it integrated “aspects of paleontology, cellular and molecular biology, developmental biology, and more. We’re looking at the problem from more than one angle, utilizing all of these methods to solve the puzzle.”

When mammalian middle ear bones develop, they begin as part of the arch of cartilage that makes up the embryonic jaw. In reptiles, these structures remain connected to the jaw as developmental processes gradually convert the cartilage to bone. In mammals, cells within a section of the developing jaw called Meckel’s cartilage disappear as the animal grows, freeing the malleus and incus (the hammer and anvil) to reach their positions in the middle ear.

To get a better idea of how the mammalian ear might have evolved, Sears, Urban and their colleagues chose to study the gray short-tailed opossum, a small and charismatic South American marsupial whose key stages of jaw and ear development take place gradually and after birth.

The group first detailed the anatomical progression of middle ear development in their opossums, capturing images that revealed the changing architecture of cartilage and bone. They observed that the progression of structures in the developing opossum jaw and ear appeared to re-enact the evolutionary progression of these structures in the mammalian fossil record.

“It was truly remarkable how well the developmental stages of our extant opossum model organism matched up with the transitional fossils . . . this makes our study organism, the gray short-tailed opossum, a fantastic living model to aid in the understanding of development of long extinct taxa,” Urban said. “By using this modern analogue, we can learn so much more about these earlier species and the origins of mammals.”

The team also explored changes in gene activity and individual cells that occurred during the breakdown of Meckel’s cartilage. They identified a set of genes whose increased activity was correlated with the self-destruction of the cells that connect the future jaw to the future ear.

Among these genes, the researchers focused on a gene called TGF-β for further investigation. When they treated developing opossums with a drug that blocks the signaling of the TGF-β protein, the death of cells within Meckel’s cartilage was prevented, and the malleus and incus remained a part of the jaw. With one tweak of gene activity, this one detail of anatomy appeared to have slid backward through evolutionary time.

TGF-β signaling is also known to play a role in the middle ear development of mice. However, the breakdown of cells in Meckel’s cartilage in this study of opossums occurred via a different mechanism than that observed in mice: the cells self-destructed, rather than being engulfed by other cells.

“It was both surprising and intriguing to find evidence suggesting that two different cellular mechanisms may be responsible for separating middle ear elements from the jaw in placental and marsupial mammals . . . combined with previous fossil evidence, this implies the [mammalian middle ear] has independently evolved at least four times in total,” Urban said. “This would initially seem improbable, except that when we performed functional testing, we showed that this connection (between the middle ear and jaw) can actually be preserved or broken by a relatively minor change in the expression of a single gene.”

This power of a single molecular change, one that could be produced by a chance mutation in a key gene, to alter the trajectory of development provides one possible answer for how the ear might have evolved. Although the group’s present study did not address why this change might have been adaptive, Urban offered one hypothesis to explain the successful spread through multiple populations of early mammals that roughly resembled his mealworm-munching opossums.

“The improved auditory sensitivity of these newly freed middle ear ossicles would have been a remarkable boon for early mammals. Most of these would have been very small, nocturnal insectivores,” he said. “Confinement to activity during the night hours would have helped them avoid becoming prey, while at the same time, improved hearing would have aided in their own predatory abilities.”

Talk:Hearing - Outer Ear Development

J Anat. 2016 Feb228(2):217-32. doi: 10.1111/joa.12344. Epub 2015 Jul 30.

The mammalian ear is a complex structure divided into three main parts: the outer middle and inner ear. These parts are formed from all three germ layers and neural crest cells, which have to integrate successfully in order to form a fully functioning organ of hearing. Any defect in development of the outer and middle ear leads to conductive hearing loss, while defects in the inner ear can lead to sensorineural hearing loss. This review focuses on the development of the parts of the ear involved with sound transduction into the inner ear, and the parts largely ignored in the world of hearing research: the outer and middle ear. The published data on the embryonic origin, signalling, genetic control, development and timing of the mammalian middle and outer ear are reviewed here along with new data showing the Eustachian tube cartilage is of dual embryonic origin. The embryonic origin of some of these structures has only recently been uncovered (Science, 339, 2013, 1453 Development, 140, 2013, 4386), while the molecular mechanisms controlling the growth, structure and integration of many outer and middle ear components are hardly known. The genetic analysis of outer and middle ear development is rather limited, with a small number of genes often affecting either more than one part of the ear or having only very small effects on development. This review therefore highlights the necessity for further research into the development of outer and middle ear structures, which will be important for the understanding and treatment of conductive hearing loss. KEYWORDS: Eustachian tube cartilage development embryonic origin external auditory meatus middle ear ossicles outer ear tympanic membrane

PMID: 26227955 PMCID: PMC4718165 DOI: 10.1111/joa.12344

Developmental mechanisms of the tympanic membrane in mammals and non-mammalian amniotes

Congenit Anom (Kyoto). 2016 Jan56(1):12-7. doi: 10.1111/cga.12132.

Takechi M1, Kitazawa T2,3, Hirasawa T4, Hirai T4, Iseki S1, Kurihara H2,5,3, Kuratani S4.

The tympanic membrane is a thin layer that originates from the ectoderm, endoderm, and mesenchyme. Molecular-genetic investigations have revealed that interaction between epithelial and mesenchymal cells in the pharyngeal arches is essential for development of the tympanic membrane. We have recently reported that developmental mechanisms underlying the tympanic membrane seem to be different between mouse and chicken, suggesting that the tympanic membrane evolved independently in mammals and non-mammalian amniotes. In this review, we summarize previous studies of tympanic membrane formation in the mouse. We also discuss its formation in amniotes from an evolutionary point of view. © 2015 Japanese Teratology Society. KEYWORDS: Goosecoid middle ear morphological evolution pharyngeal arch tympanic membrane

Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids

Nat Commun. 2015 Apr 226:6853. doi: 10.1038/ncomms7853.

Kitazawa T1, Takechi M2, Hirasawa T3, Adachi N3, Narboux-Nême N4, Kume H5, Maeda K6, Hirai T3, Miyagawa-Tomita S6, Kurihara Y1, Hitomi J7, Levi G4, Kuratani S3, Kurihara H8.

The amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain unknown. Here we show that lower-to-upper jaw transformation induced by inactivation of the Endothelin1-Dlx5/6 cascade involving Goosecoid results in loss of the tympanic membrane in mouse, but causes duplication of the tympanic membrane in chicken. Detailed anatomical analysis indicates that the relative positions of the primary jaw joint and first pharyngeal pouch led to the coupling of tympanic membrane formation with the lower jaw in mammals, but with the upper jaw in diapsids. We propose that differences in connection and release by various pharyngeal skeletal elements resulted in structural diversity, leading to the acquisition of the tympanic membrane in two distinct manners during amniote evolution.

Movement of the external ear in human embryo

Head Face Med. 2012 Feb 18:2.

Kagurasho M, Yamada S, Uwabe C, Kose K, Takakuwa T. Source Human Health Science, Graduate School of Medicine, Kyoto University, 606-8507, Shogoin Kawahara-cyo 53, Kyoto, Japan.

INTRODUCTION: External ears, one of the major face components, show an interesting movement during craniofacial morphogenesis in human embryo. The present study was performed to see if movement of the external ears in a human embryo could be explained by differential growth. METHODS: In all, 171 samples between Carnegie stage (CS) 17 and CS 23 were selected from MR image datasets of human embryos obtained from the Kyoto Collection of Human Embryos. The three-dimensional absolute position of 13 representative anatomical landmarks, including external and internal ears, from MRI data was traced to evaluate the movement between the different stages with identical magnification. Two different sets of reference axes were selected for evaluation and comparison of the movements. RESULTS: When the pituitary gland and the first cervical vertebra were selected as a reference axis, the 13 anatomical landmarks of the face spread out within the same region as the embryo enlarged and changed shape. The external ear did move mainly laterally, but not cranially. The distance between the external and internal ear stayed approximately constant. Three-dimensionally, the external ear located in the caudal ventral parts of the internal ear in CS 17, moved mainly laterally until CS 23. When surface landmarks eyes and mouth were selected as a reference axis, external ears moved from the caudal lateral ventral region to the position between eyes and mouth during development. CONCLUSION: The results indicate that movement of all anatomical landmarks, including external and internal ears, can be explained by differential growth. Also, when the external ear is recognized as one of the facial landmarks and having a relative position to other landmarks such as the eyes and mouth, the external ears seem to move cranially.

© 2012 Kagurasho et al licensee BioMed Central Ltd.

A missense mutation in PPARD causes a major QTL effect on ear size in pigs

PLoS Genet. 2011 May7(5):e1002043. Epub 2011 May 5.

Ren J, Duan Y, Qiao R, Yao F, Zhang Z, Yang B, Guo Y, Xiao S, Wei R, Ouyang Z, Ding N, Ai H, Huang L. Source Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, China.

Chinese Erhualian is the most prolific pig breed in the world. The breed exhibits exceptionally large and floppy ears. To identify genes underlying this typical feature, we previously performed a genome scan in a large scale White Duroc × Erhualian cross and mapped a major QTL for ear size to a 2-cM region on chromosome 7. We herein performed an identical-by-descent analysis that defined the QTL within a 750-kb region. Historically, the large-ear feature has been selected for the ancient sacrificial culture in Erhualian pigs. By using a selective sweep analysis, we then refined the critical region to a 630-kb interval containing 9 annotated genes. Four of the 9 genes are expressed in ear tissues of piglets. Of the 4 genes, PPARD stood out as the strongest candidate gene for its established role in skin homeostasis, cartilage development, and fat metabolism. No differential expression of PPARD was found in ear tissues at different growth stages between large-eared Erhualian and small-eared Duroc pigs. We further screened coding sequence variants in the PPARD gene and identified only one missense mutation (G32E) in a conserved functionally important domain. The protein-altering mutation showed perfect concordance (100%) with the QTL genotypes of all 19 founder animals segregating in the White Duroc × Erhualian cross and occurred at high frequencies exclusively in Chinese large-eared breeds. Moreover, the mutation is of functional significance it mediates down-regulation of β-catenin and its target gene expression that is crucial for fat deposition in skin. Furthermore, the mutation was significantly associated with ear size across the experimental cross and diverse outbred populations. A worldwide survey of haplotype diversity revealed that the mutation event is of Chinese origin, likely after domestication. Taken together, we provide evidence that PPARD G32E is the variation underlying this major QTL.

Ear reconstruction through tissue engineering

Adv Otorhinolaryngol. 201068:108-19. Epub 2010 May 3.

Department of Otorhinolaryngology, Head and Neck Surgery Campus Benjamin Franklin, Charité University Medicine Berlin, Berlin, Germany. [email protected] Abstract For decades, reconstructive surgery of the auricle has presented a challenge to surgeons. An immense number of publications now document the efforts to develop and improve techniques designed to provide reasonable shape and functionality. Since the early 1990s, tissue engineering has become increasingly popular in the field of reconstructive surgery. In particular, when an in-vitro-manufactured auricular-shaped cartilage implant was implanted on the back of a nude mouse, reconstructive surgeons were intrigued and patients' expectations were raised. However, almost 20 years after tissue engineering was defined by Langer and Vacanti [Science 1993260:920-926] as: 'an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ', only single case reports have been published. These reports detail the clinical application of in-vitro-manufactured cartilage for reconstructive procedures in the head and neck. The present article describes the fundamentals and potential of tissue engineering in reconstructive surgery of the auricle, and highlights the limitations that prevent its current clinical application.

Copyright 2010 S. Karger AG, Basel. PMID: 20442565

Combined reconstruction of congenital auricular atresia and severe microtia

Adv Otorhinolaryngol. 201068:95-107. Epub 2010 May 3.

Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Prosper Hospital, Ruhr University Bochum, Recklinghausen, Germany. [email protected] Abstract OBJECTIVES: Due to their embryological development, auricular atresia and severe microtia are, in most cases, combined malformations. The aims of this study were firstly to develop a surgical technique for combined esthetic and functional reconstruction with a minimum of operations and secondly to evaluate its results.

STUDY DESIGN: Prospective clinical evaluation.

PATIENTS AND METHODS: Fifty-two patients with third-degree microtia and congenital aural atresia with a sound-conducting block of about 50 dB were treated. In the first operation, autogenous cartilage was harvested, and the auricular framework was fabricated and implanted. In addition, the tympanic membrane and the external ear canal were prefabricated, and stored in a subcutaneous pocket. In the second step, the elevation of the new framework was combined with the operation for atresia, utilizing the prefabricated tympanic membrane and external ear canal. In the third step, the cavum concha was deepened, and the external ear canal was opened and covered with a skin graft.

RESULTS: In total, 76% of the patients had a final conductive hearing loss of 30 dB or less. No restenosis of the new external ear canal was observed. The esthetic results of the constructed auricles are shown in this report.

CONCLUSION: With this combination of plastic surgery for the auricle and functional surgery for the middle ear, no additional operations are necessary and the prefabrication of the external ear canal and the tympanic membrane gives stable and reliable results. This combined technique offers the best chance of optimal esthetic and functional rehabilitation for patients with these malformations.

Copyright 2010 S. Karger AG, Basel. PMID: 20442564

Morphology of the human tympanic membrane annulus

Otolaryngol Head Neck Surg. 2010 May142(5):682-7.

Kassem F, Ophir D, Bernheim J, Berger G.

Department of Otolaryngology-Head and Neck Surgery, Meir Medical Center, Kfar Saba, Israel. [email protected] Abstract OBJECTIVE: To study the full panoramic view with figuring of the morphology and topography of the human tympanic annulus.

STUDY DESIGN: Postmortem material analysis.

SETTING: University-affiliated hospital.

SUBJECTS AND METHODS: Twenty-three single, normal human adult tympanic membranes were completely extracted from formalin-fixed temporal bones. They were faced medially and placed at the same level of a graph paper mounted on a board. High-quality images of the tissue preparations were taken, and computer-aided measurements of the annular caliber were calculated at nine reference points. The 6 o'clock direction served as a midpoint, and another four reference points were set anteriorly and posteriorly in clockwise and counterclockwise directions.

RESULTS: The annulus has a horseshoe-like shape with a small part absent above the neck of the malleus. The maximal mean caliber at the manubrial axis (6 o'clock direction) was 748 +/- 201 mum. The annulus gradually thins out almost symmetrically anteriorly and posteriorly, until it reaches about 15 percent of the maximal caliber at its end points (152 +/- 87 and 113 +/- 42 mum, respectively). Significant differences were found between adjacent reference points on both anterior and posterior sides.

CONCLUSIONS: The annulus has a horseshoe-like shape and gradually thins out almost symmetrically, reaching anteriorly and posteriorly about 15 percent of the maximal caliber at the manubrial axis. These new data may provide guidance in transcanal middle ear exploration and suggest the possibility of varied functions attributable to the annulus regarding middle ear sound transmission and TM vibratory properties. The data may contribute to understanding the development of marginal perforations and posterior superior retraction pockets.

Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved. PMID: 20416456

Craniofacial Microsomia Overview

Heike CL, Hing AV. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle 1993-. 2009 Mar 19.

Excerpt Disease characteristics. Craniofacial microsomia (CFM) includes a spectrum of malformations primarily involving structures derived from the first and second branchial arches. Findings include facial asymmetry resulting from maxillary and/or mandibular hypoplasia preauricular or facial tags ear malformations that can include microtia (hypoplasia of the external ear), anotia (absence of the external ear), or aural atresia (absence of the external ear canal) and hearing loss. Severity can range from subtle facial asymmetry with a small skin tag in front of an otherwise normal-appearing ear to bilateral involvement (typically asymmetric), microtia/anotia with atresia of the ear canals, microphthalmia, and respiratory compromise from severe mandibular hypoplasia. Other craniofacial malformations including cleft lip and/or palate can be seen. Non-craniofacial malformations, especially vertebral, cardiac, and limb, can be seen. Diagnosis/testing. The diagnosis of CFM is based on clinical findings. Genetic counseling. CFM most frequently occurs as a simplex case (i.e., occurrence in a single individual in a family) with unknown etiology recurrence risks are empiric. If an individual with CFM is found to have an inherited or de novo chromosome abnormality, genetic counseling for that condition is indicated. Occasional autosomal dominant or autosomal recessive inheritance is observed. If a proband has CFM and no reported family history of CFM, the risk to sibs is two to three percent this may be an underestimate because of the difficulty of obtaining an accurate family history for some of the subtle features of CFM. Management. Treatment of manifestations: For optimal outcome children with CFM require timely and coordinated assessments and interventions. Ideally, children should be managed by an experienced multidisciplinary craniofacial team. The goals of treatment for CFM are to assure adequate respiratory support and feeding in infants with severe facial malformations, maximize hearing and communication, improve facial symmetry, and optimize dental occlusion. Treatment is age-dependent, with time-sensitive interventions at appropriate stages of craniofacial growth and development. Copyright © 1993-2010, University of Washington, Seattle. All rights reserved.

Congenital upper auricular detachment: Report of two unusual cases

Indian J Plast Surg. 2009 Jul42(2):265-8.

Plastic Surgery Unit, Department of Surgery, Netaji Subhash Chandra Bose Government Medical College, Jabalpur-482 003, MP, India. Abstract Two unusual cases of congenital bilateral ear deformity have been presented. The deformity is characterized by upper auricular detachment on the right side with anotia on the left side in the first case and upper auricular detachment on the left side with normal ear on the right side in the second case. An attempt has been made to correlate the presented deformity with the embryological - foetal development of the auricle. Satisfactory correction can be obtained by repositioning the auricle back in to its normal position.

The kidney and ear: emerging parallel functions

Departments of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. Abstract The association between renal dysplasia and minor malformations of the external ear is weak. However, there is a remarkable list of syndromes that link the kidney to the inner ear. To organize these seemingly disparate syndromes, we cluster representative examples into three groups: (a) syndromes that share pathways regulating development (b) syndromes involving dysfunction of the primary cilium, which normally provides critical information to epithelial cells about the fluid in which they are bathed (c) syndromes arising from dysfunction of specialized proteins that transport ions and drugs in and out of the extracellular fluid or provide structural support.

Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular syndrome

Am J Hum Genet. 2008 May82(5):1178-84.

Schorderet DF, Nichini O, Boisset G, Polok B, Tiab L, Mayeur H, Raji B, de la Houssaye G, Abitbol MM, Munier FL.

Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland. [email protected] Abstract Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (microcornea, microphthalmia, anterior-segment dysgenesis, cataract, coloboma of various parts of the eye, abnormalities of the retinal pigment epithelium, and rod-cone dystrophy) and a particular cleft ear lobule. Linkage analysis and mutation screening revealed in the first exon of the NKX5-3 gene a homozygous 26 nucleotide deletion, generating a truncating protein that lacked the complete homeodomain. Morpholino knockdown expression of the zebrafish nkx5-3 induced microphthalmia and disorganization of the developing retina, thus confirming that this gene represents an additional member implicated in axial patterning of the retina.

Human ears grow throughout the entire lifetime according to complicated and sexually dimorphic patterns--conclusions from a cross-sectional analysis

Anthropol Anz. 2007 Dec65(4):391-413.

Niemitz C, Nibbrig M, Zacher V.

Institute for Human Biology and Physical Anthropology, Freie Universität Berlin, Germany. [email protected] Abstract In most of its anatomical constituents, e.g. in the Helix, etc., the external human ear is homologous to that of all Primates and Scandentia (tree shrews). Thus, its genetic basis is largely older than 60 Mio yrs. Based upon the observation of lifelong growth of the ear (e.g. Montacer-Kuhssary 1959), we aimed to elucidate the growth of the human ear in a more detailed way throughout life and in both sexes. On standardized photographical material collected randomly in Berlin (Germany), we measured N = 1448 ears from neonate children to volunteers of 92 yrs in age. 10 longitudinal measurements and 5 further anatomical parameters yielded a data set of roughly 19,000 data in total. Based upon our cross-section analysis, we quantified several sexual dimorphisms. Furthermore, we deduced ontogenetic developments and, partially, corrected their proportions for secular acceleration and body height shrinking with age. At the time of birth, in proportion to the body, the external ear was even bigger than the large head and continued growing rather linearly throughout life, reaching the highest average lengths in the volunteers aged over 85 yrs. The large yearly increases during childhood began to diminish at as early an age as 8 or 10 yrs. In all parameters where post adult growth was observed, female ears showed a lesser increase than those of men. The greatest ear length in females was 52 mm (SD +/- 4.3 mm) at birth, 61 mm (SD +/- 3.9 mm) at around 20 yrs of age and 72 mm (SD +/- 4.6 mm) in women older than 70 yrs. For the male subjects, these three values were: 52 mm (SD +/- 4.1 mm), 65 mm (SD +/- 4.0 mm) and 78 mm (SD +/- 4.8 mm), respectively. In spite of extreme premature growth of the auricle and its further lifelong growth, three anatomical features of the ear did practically not grow at all after birth: the width of the Concha auriculae and of the Incisura intertragica, as well as the diameter of the helical brim of the auricle. The problems arising concerning the functions and selective values of all these very unusual proportions and growths are discussed. The ontogenetic development of one or more pretragal skin folds could be used as a contribution to age estimations in forensic anthropology.

The embryologic development of the human external auditory meatus. Preliminary report

Acta Otolaryngol. 1992112(3):496-503.

Nishimura Y, Kumoi T. Source Department of Otorhinolaryngology, Hyogo College of Medicine, Nishinomiya, Japan.

During the final period of embryogenesis, a funnel-shaped tube continues medially into the mesenchymal tissue forming a curved path. Although this may sound simple, the development occurring during early fetal life is in fact very complex. At first, ectodermal cells proliferate to fill the lumen of the meatus, forming the meatal plug, and then at 10 weeks the bottom of the plug extends in a disc-like fashion, so that in the horizontal plane the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. At the same time, the plug in the proximal portion of the neck starts to be resorbed. In the 13-week fetus, the disc-like plug begins to show signs of its final destiny the innermost surface of the plug in contact with the anlage of the malleus is ready to contribute to the formation of the tympanic membrane. In the 15-week fetus, the innermost portion of the disc-like plug splits, leaving a thin ectodermal cell layer of immature tympanic membrane. The neck of the boot forms the border between the primary and secondary meatus, and is the last part to split. In the 16.5-week fetus, the meatus is fully patent throughout its entire length, although the lumen is still narrow and curved. In the 18-week fetus, the meatus is already fully expanded to its complete form.


Malleus (left) A. From behind. B. From within.

The malleus develops from the first pharyngeal arch cartilage (Meckel's cartilage) and was named from its resemblance to a hammer.

The structure of the adult bone can be divided into a head, neck, and three processes (manubrium, anterior and lateral processes). In the fetus, of the three processes the anterior process is the longest and is in direct continuity with Meckel's cartilage.

Malleus ossification is initiated in the fetal period. Η] ⎖]

The newborn and infant malleus head normally contains bone marrow, that is eventually replaced by bone. ⎗]

Malleus Development (timing from ⎖] )

  • 16 weeks - two cortical fascicles situated in the neck
  • 21 weeks - fascicles extend towards the head
  • 23 weeks - extend towards to the lateral process
  • 24 weeks - extend towards to the handle
  • 29 weeks - in the handle force lines are transmitted via three cardinal fascicles (two of them via the cortical fascicle and one via the centre)
  • 31 weeks - consolidated by this time


A series of different abnormalities of the anterior process and manubrium mallei (malleus handle) have been described. ⎘]