Comparative morphology of the amphibian opercularis system: I. General design features and functional interpretation

The morphology of the opercularis system of anuran and caudate amphibians suggests that it acts to produce motion of the operculum that in turn produces fluid motion within the inner ear. The operculum and opercularis muscle form a lever system, with a narrow connection between the operculum and otic capsule acting as a fulcrum about which the operculum moves in response to forces applied via the muscle. The opercula of many species possess a muscular process on which the muscle inserts, thereby increasing the moment arm through which the muscle acts. The tonicity of the opercularis muscle allows tensile forces produced by substrate vibration or other mechanical energy applied to the forelimb to be effectively transmitted to the operculum; the elasticity of the connective tissue holding the operculum in place should act to return the operculum to its original position. The opercularis systems of frogs and non-plethodontid salamanders are similar structurally and functionally; that of plethodontid salamanders is structurally distinct but also functions as a lever system. Fluid motion produced by opercular motion could stimulate various end organs of the inner ear; the saccule, lagena, and amphibian papilla are in close approximation and wave energy could directly affect their otoconial or tectorial structures. In those anurans with a tympanic ear, the stapedial footplate and operculum articulate, but this articulation allows both to move independently. The stapes-tympanum complex and opercularis system therefore appear to be independent functional systems, and it is unlikely that the opercularis system modulates middle ear responsiveness. The general design of the opercularis system is consistent with a function in reception of substrate vibrations.     

Evolution of the mammalian middle ear.

The structure and evolution of the mandible, suspensorium, and stapes of mammal-like reptiles and early mammals are examined in an attempt to determine how, why, and when in phylogeny the precursors of the mammalian tympanic bone, malleus, and incus (postdentary jaw elements and quadrate) came to function in the reception of air-borne sound. The following conclusions are reached: It is possible that at no stage in mammalian phylogeny was there a middle ear similar to that of "typical" living reptiles, with a postquadrate tympanic membrane contracted by an extrastapes. The aquamosal sulcus of cynodonts and other therapsids, usually thought to have housed a long external acoustic meatus, possibly held a depressor mandibulae muscle. In therapsids an air-filled chamber (recessus mandibularis of Westoll) extended deep to the reflected lamina and into the depression (external fossa) on the outer aspect of the angular element. A similar chamber was present in sphenacodontids but pterygoideus musculature occupied the small external fossa. The thin tissues superficial to the recessus mandibularis served as eardrum. Primitively, vibrations reached the stapes mainly via the anterior hyoid cornu, but in dicynodonts, therocephalians, and cynodants vibrations passed mainly or exclusively from mandible to quadrate to stapes and the reflected lamina was a component of the eardrum. In the therapsid phase of mammalian phylogeny, auditory adaptation was an important aspect of jaw evolution. Auditory efficiency, and sensitivity to higher sound frequencies were enhanced by diminution and loosening of the postdentary elements and quadrate, along with transference of musculature from postdentary elements to the dentary. These changes were made possible by associated modifications, including posterior expansion of the dentary. Establishment of a dentary-squamosal articulation permitted continuation of these trends, leading to the definitive mammalian condition, with no major change in auditory mechanism except that in most mammals (not monotremes) the angular, as tympanic, eventually bcame a non-vibrating structure.     

An X-radiographic and SEM study of the osseous inner ear of multituberculates and monotremes (Mammalia): implications for mammalian phylogeny and evolution of hearing

Multituberculate petrosals with well-preserved, three-dimensional internal anatomy from the Late Cretaceous/early Paleocene Bug Creek Anthills, Montana, U.S.A., are described from X-radiographic and SEM images, as well as from conventional visual observations, and are compared with the anatomy of the osseous inner ear in monotremes and in primitive non-therian and therian mammals. Results of this study indicate that: (1) the cochlea of at least some multituberculates retained a lagena, previously known only in monotremes among mammals; (2) an enlarged vestibule evolved in several lineages of multituberculates independently, and hence is not a synapomorphy of the order; (3) the cochlear canal lacks osseous laminae in support of the short, wide basilar membrane, which was probably inefficient in responding to high-frequency airborne vibrations; and (4) consequently, bone-conducted hearing in some multituberculate species may have been important in interpretation of their surroundings. Comparisons with the inner ear of monotremes and primitive therians indicate that curvature of the cochlea and cribriform plates for passage of vestibulocochlear nerve branches through the petrosal are unlikely homologues between monotremes and therians. From non-therian to therian mammals, there is a distinct morphological gap in the inner ear transition, characterized by acquisition of a number of neomorphs in the therian inner ear; an intermediate stage has yet to be discovered.     

STRUCTURE AND FUNCTION IN WHALE EARS

ABSTRACT

Ultrasonic echolocation abilities are well documented in several dolphin species, but hearing characteristics are unknown for most whales. Vocalization data suggest whale hearing spans infra- to ultrasonic ranges. This paper presents an overview of whale ear anatomy and analyzes 1) how whale ears are adapted for underwater hearing and 2) how inner ear differences relate to different hearing capacities among whales.

Whales have adaptations for rapid, deep diving and long submersion; e.g., broad- bore Eustachian tubes, no pinnae, and no air-filled external canals, that impact sound reception. In odontocetes, two soft tissue channels conduct sound to the ear. In mysticetes, bone and soft tissue conduction are likely. The middle ear is air-filled but has an extensible mucosa. Cochlear structures are hypertrophied and vestibular components are reduced. Auditory ganglion cell densities are double land mammal averages (2000–4000/mm). Basilar membrane lengths range 20–70 mm; gradients are larger than in terrestrial mammals. Odontocetes have 20–60% bony membrane support and basal ratios >0.6, consistent with hearing >150 kHz. Mysticetes have apical ratios <0.002 and no bony lateral support, implying acute infrasonic hearing. Cochlear hypertrophy may be adaptive for high background noise. Vestibular loss is consistent with cervical fusion. Exceptionally high auditory fiber counts suggest both mysticetes and odontocetes have ears “wired” for more complex signal processing mechanisms than most land mammals.     

Tonotopically arranged traveling waves in the miniature hearing organ of bushcrickets

Place based frequency discrimination (tonotopy) is a fundamental property of the coiled mammalian cochlea. Sound vibrations mechanically conducted to the hearing organ manifest themselves into slow moving waves that travel along the length of the organ, also referred to as traveling waves. These traveling waves form the basis of the tonotopic frequency representation in the inner ear of mammals. However, so far, due to the secure housing of the inner ear, these waves only could be measured partially over small accessible regions of the inner ear in a living animal. Here, we demonstrate the existence of tonotopically ordered traveling waves covering most of the length of a miniature hearing organ in the leg of bushcrickets in vivo using laser Doppler vibrometery. The organ is only 1 mm long and its geometry allowed us to investigate almost the entire length with a wide range of stimuli (6 to 60 kHz). The tonotopic location of the traveling wave peak was exponentially related to stimulus frequency. The traveling wave propagated along the hearing organ from the distal (high frequency) to the proximal (low frequency) part of the leg, which is opposite to the propagation direction of incoming sound waves. In addition, we observed a non-linear compression of the velocity response to varying sound pressure levels. The waves are based on the delicate micromechanics of cellular structures different to those of mammals. Hence place based frequency discrimination by traveling waves is a physical phenomenon that presumably evolved in mammals and bushcrickets independently.     

Middle ear transmission in the grass frog, Rana temporaria

The anuran middle ear serves to transmit eardrum vibrations to the inner ear. In order to do this efficiently, the eardrum and middle ear must operate as an impedance transformer matching the low impedance of air to the higher impedance of the fluid-filled inner ear. In amniotes, one of the mechanisms used to achieve impedance transformation is to have the middle ear work as a force-amplifying lever system. Here, we present evidence that the grass frog middle ear also implements a lever system. The columellar footplate, which sits in the oval window, is firmly connected to the otic capsule along its ventral edge. Therefore, simple in-out movement of the columella is prevented while a rotational movement around the footplate's ventral edge is possible. The latter movement pattern was confirmed by laser vibrometry measurements of eardrum and footplate vibrations. The results showed that the footplate vibrations were 20–30 dB weaker than those of the eardrum and that the two structures vibrated 180° out of phase (at low frequencies). The lever ratio was approximately 6, i.e. somewhat higher than lever ratios reported for amniotes. Hence, the middle ear lever probably makes a significant contribution to impedance matching in frogs. Accepted: 1 July 1997     

Infrasonic hearing in birds: a review of audiometry and hypothesized structure–function relationships

The perception of airborne infrasound (sounds below 20 Hz, inaudible to humans except at very high levels) has been documented in a handful of mammals and birds. While animals that produce vocalizations with infrasonic components (e.g. elephants) present conspicuous examples of potential use of infrasound in the context of communication, the extent to which airborne infrasound perception exists among terrestrial animals is unclear. Given that most infrasound in the environment arises from geophysical sources, many of which could be ecologically relevant, communication might not be the only use of infrasound by animals. Therefore, infrasound perception could be more common than currently realized. At least three bird species, each of which do not communicate using infrasound, are capable of detecting infrasound, but the associated auditory mechanisms are not well understood. Here we combine an evaluation of hearing measurements with anatomical observations to propose and evaluate hypotheses supporting avian infrasound detection. Environmental infrasound is mixed with non‐acoustic pressure fluctuations that also occur at infrasonic frequencies. The ear can detect such non‐acoustic pressure perturbations and therefore, distinguishing responses to infrasound from responses to non‐acoustic perturbations presents a great challenge. Our review shows that infrasound could stimulate the ear through the middle ear (tympanic) route and by extratympanic routes bypassing the middle ear. While vibration velocities of the middle ear decline towards infrasonic frequencies, whole‐body vibrations – which are normally much lower amplitude than that those of the middle ear in the ‘audible’ range (i.e. >20 Hz) – do not exhibit a similar decline and therefore may reach vibration magnitudes comparable to the middle ear at infrasonic frequencies. Low stiffness in the middle and inner ear is expected to aid infrasound transmission. In the middle ear, this could be achieved by large air cavities in the skull connected to the middle ear and low stiffness of middle ear structures; in the inner ear, the stiffness of round windows and cochlear partitions are key factors. Within the inner ear, the sizes of the helicotrema and cochlear aqueduct are expected to play important roles in shunting low‐frequency vibrations away from low‐frequency hair‐cell sensors in the cochlea. The basilar papilla, the auditory organ in birds, responds to infrasound in some species, and in pigeons, infrasonic‐sensitive neurons were traced back to the apical, abneural end of the basilar papilla. Vestibular organs and the paratympanic organ, a hair cell organ outside of the inner ear, are additional untested candidates for infrasound detection in birds. In summary, this review brings together evidence to create a hypothetical framework for infrasonic hearing mechanisms in birds and other animals.     

Experimental and Theoretical Explorations of Traveling Waves and Tuning in the Bushcricket Ear

The ability to detect airborne sound is essential for many animals. Examples from the inner ear of mammals and bushcrickets demonstrate that similar detection strategies evolved in taxonomically distant species. Both mammalian and bushcricket ears possess a narrow strip of sensory tissue that exhibits an anatomical gradient and traveling wave motion responses used for frequency discrimination. We measured pressure and motion in the bushcricket ear to investigate physical properties, stiffness, and mass, which govern the mechanical responses to sound. As in the mammalian cochlea, sound-induced fluid pressure and motion responses were tonotopically organized along the longitudinal axis of the crista acustica, the bushcricket’s hearing organ. The fluid pressure at the crista and crista motion were used to calculate the acoustic impedance of the organ-bounded fluid mass (Z_mass). We used a theoretical wave analysis of wavelength data from a previous study to predict the crista acustica stiffness. The wave analysis also predicts Z_mass, and that result agreed reasonably well with the directly measured Z_mass, lending support to the theoretical wave analysis. The magnitude of the crista stiffness was similar to basilar membrane stiffness in mammals, and as in mammals, the stiffness decreased from the high-frequency to the low-frequency region. At a given location, the stiffness increased with increasing frequency, corresponding to increasing curvature of the traveling wave (decreasing wavelength), indicating that longitudinal coupling plays a substantial role in determining crista stiffness. This is in contrast to the mammalian ear, in which stiffness is independent of frequency and longitudinal coupling is relatively small.     

Morphology of the middle ear of golden moles (Chrysochloridae)

The middle ear structures of nine species of golden moles (family Chrysochloridae) were examined under the light microscope. Auditory structures of several of these species are described here for the first time in detail, the emphasis being on the ossicular apparatus. Confirming previous observations, some golden moles (e.g. Amblysomus species) have ossicles of a morphology typical of mammals, whereas others ( Chrysospalax , Chrysochloris , Cryptochloris and Eremitalpa species) have enormously hypertrophied mallei. Golden moles differ in the nature and extent of the interbullar connection, the shape of the tympanic membrane and that of the manubrium. The stapes has an unusual orientation, projecting dorsomedially from the incus. It has been proposed that hypertrophied ossicles in golden moles are adapted towards the detection of seismic vibrations. The functional morphology of the middle ear apparatus is reconsidered in this light, and it is proposed that adaptations towards low-frequency airborne hearing might have predisposed golden moles towards the evolution of seismic sensitivity through inertial bone conduction. The morphology of the middle ear apparatus sheds little light on the disputed ordinal position of the Chrysochloridae.     

Environmental influences in the evolution of tetrapod hearing sensitivity and middle ear tuning

Vertebrates inhabit and communicate acoustically in most natural environments. We review the influence of environmental factors on the hearing sensitivity of terrestrial vertebrates, and on the anatomy and mechanics of the middle ears. Evidence suggests that both biotic and abiotic environmental factors affect the evolution of bandwidth and frequency of peak sensitivity of the hearing spectrum. Relevant abiotic factors include medium type, temperature, and noise produced by nonliving sources. Biotic factors include heterospecific, conspecific, or self-produced sounds that animals are selected to recognize, and acoustic interference by sounds that other animals generate. Within each class of tetrapods, the size of the middle ear structures correlates directly to body size and inversely to frequency of peak sensitivity. Adaptation to the underwater medium in cetaceans involved reorganization of the middle ear for novel acoustic pathways, whereas adaptation to subterranean life in several mammals resulted in hypertrophy of the middle ear ossicles to enhance their inertial mass for detection of seismic vibrations. The comparative approach has revealed a number of generalities about the effect of environmental factors on hearing performance and middle ear structure across species. The current taxonomic sampling of the major tetrapod groups is still highly unbalanced and incomplete. Future expansion of the comparative evidence should continue to reveal general patterns and novel mechanisms.     

Palmated antlers of moose may serve as a parabolic reflector of sounds

It has been postulated that the excellent sense of hearing in moose is mostly due to: (1) the large surface of the external ear, (2) better stereophony due to the large distance between ears, (3) independently movable, extremely adjustable pinna, and (4) the amplification of sounds reflected by the palms of the antlers. The last factor, possible reflection of sounds into pinna by the palm of the antlers, was tested in this study on a large antler trophy of Alaskan moose. The reception of a standard tone, broadcast from the frontally placed speaker, was recorded by a sound level meter located in an artificial moose ear. Three locations of the ear, as positioned relative to the speaker, e.g., frontward, sideward, and backward, were tested. The weakest reception was recorded in the backward position of the ear. If the sound pressure measured in the frontward position was set as 100%, the sound pressure in the backward position was 79%. The strongest reception was recorded when the artificial ear was positioned toward the center of the antler palm. In this position, the sound pressure was 119% relative to the frontward position. These findings strongly indicate that the palm of moose antlers may serve as an effective, parabolic reflector which increases the acoustic pressure of the incoming sound.     

The influence of muscles activation on the dynamical behaviour of the tympano-ossicular system of the middle ear

The human ear is a complex biomechanical system and is divided into three parts: outer, middle and inner ear. The middle ear is formed by ossicles (malleus, incus and stapes), ligaments, muscles and tendons, which transfers sound vibrations from the eardrum to the inner ear, linking with mastoid and Eustachian tube. In this work, a finite element modelling of the tympano-ossicular system of the middle ear was developed. A dynamic study based on a structural response to harmonic vibrations, for a sound pressure level (SPL) of 110, 120 and 130 dB SPL applied in the eardrum, is presented. The connection between the ossicles is made using a contact formulation. The model includes the different ligaments considering its hyperelastic behaviour. The activation of the muscles is based on the constitutive model proposed by previous work. The harmonic responses of displacement and pressure obtained on the stapes footplate, for a frequency range between 100 Hz and 10 kHz, are obtained simulating the muscle activation. The results are compared considering the passive and active states. The results are discussed and they are in accordance with audiological data published with reference to the effects of the middle ear muscles contraction.     

Hearing in the African lungfish (Protopterus annectens): pre-adaptation to pressure hearing in tetrapods?

Lungfishes are the closest living relatives of the tetrapods, and the ear of recent lungfishes resembles the tetrapod ear more than the ear of ray-finned fishes and is therefore of interest for understanding the evolution of hearing in the early tetrapods. The water-to-land transition resulted in major changes in the tetrapod ear associated with the detection of air-borne sound pressure, as evidenced by the late and independent origins of tympanic ears in all of the major tetrapod groups. To investigate lungfish pressure and vibration detection, we measured the sensitivity and frequency responses of five West African lungfish (Protopterus annectens) using brainstem potentials evoked by calibrated sound and vibration stimuli in air and water. We find that the lungfish ear has good low-frequency vibration sensitivity, like recent amphibians, but poor sensitivity to air-borne sound. The skull shows measurable vibrations above 100 Hz when stimulated by air-borne sound, but the ear is apparently insensitive at these frequencies, suggesting that the lungfish ear is neither adapted nor pre-adapted for aerial hearing. Thus, if the lungfish ear is a model of the ear of early tetrapods, their auditory sensitivity was limited to very low frequencies on land, mostly mediated by substrate-borne vibrations.     

Role of the opercularis muscle in seismic sensitivity in the bullfrog Rana catesbeiana

The inner ear of anuran amphibians appears to be exceptionally sensitive to substrate vibration. The opercularis system, consisting of an opercularis muscle running from the shoulder girdle to a movable, cartilaginous operculum lying next to the inner ear, has been hypothesized to be involved in driving these seismic responses. Removal of the opercularis muscle of adult bullfrogs, Rana catesbeiana, caused clear decreases in microphonic responses of the inner ear to vibrations from 20-250 Hz and 0.05-5.0 cm/sec2 accelerations. Degree of decrease in responsiveness was variable between individuals and between different frequencies of stimulation, ranging up to 90% reduction at certain frequencies and in certain specimens. Decreases were most marked at lower frequencies below about 50 Hz. Additional removal of the levator scapulae superior muscle, which runs alongside the opercularis muscle from the shoulder girdle to ventrolateral portions of the otic capsule, also tended to depress responses, although this effect was substantially less (generally less than 10%) and also less consistent. As the opercularis muscle appears to be derived from the levator scapulae musculature, it is speculated that primitively seismic sensitivity was enhanced by a muscular connection that could transmit motion from the forelimb to the otic region, responsiveness being further enhanced by the subsequent evolution of the specialized opercularis system.     

Specialized sound reception in dolphins—a hint for the function of the dorsal cochlear nucleus in mammals

Dolphins have developed a specialized system for sound reception. Their pinnae are reduced and shifted under the skin, and sound is transduced via the lower jaw to the auditory ossicles. In line with their auditory functions (notably echolocation), most auditory nuclei in the brain stem of dolphins are extremely well‐developed. In contrast, the dorsal cochlear nucleus is drastically reduced. In the La Plata dolphin the volume of the dorsal cochlear nucleus is 4 mm³, while that of the ventral cochlear nucleus is 98 mm³. The reduction in size of the dorsal cochlear nucleus is also seen in baleen whales, which do not echolocate and are, in contrast to dolphins, tuned to deep frequencies. However, dolphins and baleen whales have the reduction of the outer ear in common. In humans, cats, bats and seals, there is a correlation between the development of pinnae and the dorsal cochlear nucleus. So, we conclude that the function of the dorsal cochlear nucleus in mammals could be to eliminate “auditory artifacts”; arising from the operation of the pinnae.     

Three approaches for estimating the elastic modulus of the tympanic membrane

The function of the middle ear is to resolve the acoustic impedance mismatch between the air in the ear canal and the fluid of the inner ear. Without this impedance matching, very little acoustic energy would be absorbed into the cochlea. The first step in this process is the tympanic membrane (TM) converting sound in the ear canal into vibrations of the middle ear bones. Understanding how the TM manages its task so successfully over such a broad frequency range should lead to more satisfactory and less variable TM repairs (myringoplasty). In addition, understanding the mechanics of the TM is necessary to improve the coupling between ossicular prostheses and the TM. Mathematical models have played a central role in helping the research community understand the mechanics of the eardrum. However, all models require parameters as inputs. Unfortunately, most of the parameters needed for modeling the TM are not well known. In this work, several approaches for inferring the material properties of the TM are explored. First, constitutive modeling is used to estimate an elastic modulus based on the elastic modulus of collagen and experimentally observed fiber densities. Second, experimental tension and bending test results from the literature are re-interpreted using composite laminate theory. Lastly, dynamic measurements of the cat TM are used in conjunction with a composite shell model to bound the material parameters. Values from the literature, both measurement and modeling efforts, and from the present analysis are brought together to form a coherent picture of the TM's material properties. In the human, the data bound the elastic modulus between 0.1 and 0.3 GPa. In the cat, the data suggest a range of 0.1-0.4 GPa. These values are significantly higher than previous estimates.     

What did Morganucodon hear?

The structure of the middle and inner ear of Morganucodon , one of the oldest known mammals, is reviewed and compared to the structure of the ears of extant mammals, reptiles and birds with known auditory capabilities. Specifically, allometric relationships between ear dimensions (basilar-membrane length, tympanic-membrane area and stapes-footplate area) and specific features of the audiogram are defined in extant ears. These relationships are then used to make several predictions of auditory function in Morganucodon. The results point out that the ear structures of Morganucodon–Art similar in dimensions to ear structures in both extant small mammals–with predominantly high-frequency (10 kHz) auditory capabilities, and reptiles and birds- with better low and middle-frequency hearing (< 5 kHz). Although the allometric analysis cannot by itself determine whether Morganucodon heard more like present-day small mammals, or birds and reptiles, the apparent stiffness of the Morganucodon middle ear is both more consistent with the high-frequency mammalian middle ear and would act to decrease the sensitivity of a bird-reptile middle ear to low-frequency sound. Several likely hearing scenarios for Morganucodon are defined, including a scenario in which these animals had ears like those of modern small mammals that are selectively sensitive to high-frequency sounds, and a second scenario in which the Morganucodon ear was moderately sensitive to sounds of a narrow middle-frequency range (5–7 kHz) and relatively insensitive to sounds of higher or lower frequency. The evidence needed to substantiate either scenario includes some objective measure of the stiffness of the Morganucodon ossicular system, while a key datum needed to distinguish between the two hypotheses includes confirmation of the presence or absence of a cochlear lamina in the Morganucodon inner ear.     

Explanation of octave and diplacusis effects

The study is based on the model of sound perception that involves two systems of measuring the frequency of the sound being perceived. The system of analyzing the periodicity of spike sequence in axons of neurons innervating the internal auditory hair cells excited by the running wave is less precise, but it provides the estimation of the frequency of any periodical sounds. Exact measurement of the frequency of the sinusoidal sound occurs from the spikes in axons of neurones innervating the internal hair cells of the auditory reception field, which uses the entire train of waves excited by this sound in the critical layer of the waveguide of the internal ear cochlea, which corresponds to the frequency of the sound. The octave effect is explained in terms of the fact that the spectrum of frequencies of speech sounds, singing and music coincides with the region of the audibility range in which the impulses of the auditory nerve fibers are synchronized by incoming signals. The octave similarity, i.e., the similarity in the sounding of harmonic signals, whose frequencies relate as even numbers (2:1, etc.), is explained by an unambiguous match between the sound frequency and pulse rate in auditory fibers coming from the auditory reception field. The presence in the brain posterior tubercles of multipeak neurons whose peaks are in octave ratio, confirm the crucial role of the system of exact measurement of frequency in the phenomenon of octave similarity. The phenomenon of diplacusis, which is particularly pronounced in persons with Menier disease, is caused by changes in the position of the auditory reception field in the diseased ear as compared with the healthy ear. The alternating switching of reception from one ear to the other is related to a disturbance of the unitary image of pitch.     

Developmental aspects of the tympanic membrane: Shedding light on function and disease

The ear drum, or tympanic membrane (TM), is a key component in the intricate relay that transmits air‐borne sound to our fluid‐filled inner ear. Despite early belief that the mammalian ear drum evolved as a transformation of a reptilian drum, newer fossil data suggests a parallel and independent evolution of this structure in mammals. The term “drum” belies what is in fact a complex three‐dimensional structure formed from multiple embryonic cell lineages. Intriguingly, disease affects the ear drum differently in its different parts, with the superior and posterior parts being much more frequently affected. This suggests a key role for the developmental details of TM formation in its final form and function, both in homeostasis and regeneration. Here we review recent studies in rodent models and humans that are beginning to address large knowledge gaps in TM cell dynamics from a developmental biologist's point of view. We outline the biological and clinical uncertainties that remain, with a view to guiding the indispensable contribution that developmental biology will be able to make to better understanding the TM.