The human otitis media with effusion: a numerical-based study

Otitis media is a group of inflammatory diseases of the middle ear. Acute otitis media and otitis media with effusion (OME) are its two main types of manifestation. Otitis media is common in children and can result in structural alterations in the middle ear which will lead to hearing losses. This work studies the effects of an OME on the sound transmission from the external auditory meatus to the inner ear. The finite element method was applied on the present biomechanical study. The numerical model used in this work was built based on the geometrical information obtained from The visible ear project. The present work explains the mechanisms by which the presence of fluid in the middle ear affects hearing by calculating the magnitude, phase and reduction of the normalized umbo velocity and also the magnitude and phase of the normalized stapes velocity. A sound pressure level of 90 dB SPL was applied at the tympanic membrane. The harmonic analysis was performed with the auditory frequency varying from 100 Hz to 10 kHz. A decrease in the response of the normalized umbo and stapes velocity as the tympanic cavity was filled with fluid was obtained. The decrease was more accentuated at the umbo.     

Study of age-related changes in Middle ear transfer function

Abstract

Osteoporosis (OP) is common with advancing age. Several studies have shown a strong correlation between OP and otosclerosis. However, no studies have investigated OP of the malleus, incus or stapes in the human middle ear, its effect on middle ear transfer function. Here, we investigate whether these three ossicles develop OP, and how this affects middle ear transfer function. The effect of OP on middle ear transfer function was investigated in simulations based on a finite element (FE) method. First, the FE model used in our previous study was refined, and optimized by introducing viscoelastic properties to selected soft tissues of the middle ear. Then, the FE model was used to simulate OP of the three ossicles and assess its influence on middle ear transfer function. Other possible age-related changes, such as stiffness of the joints or ligaments in the middle ear, were also investigated. The results indicated that OP of the ossicles could increase the high frequency displacement of both the umbo and stapes footplate (FP). However, the stiffness of the middle ear soft tissue can lead to the decrease of middle ear gain at lower frequencies. Furthermore, loosening of these joints or ligaments could increase displacement of the umbo and stapes FP. In conclusion, although age-related hearing loss is most commonly conceived of as sensorineural hearing loss (SNHL), we found that age-related changes may also include OP and changes in joint stiffness, but these will have little effect on middle ear transfer function in elderly people.     

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     

Bone‐conduction hearing and seismic sensitivity of the late permian anomodont Kawingasaurus fossilis

An investigation of the internal cranial anatomy of the anomodont Kawingasaurus from the Upper Permian Usili Formation in Tanzania by means of neutron tomography revealed an unusual inner and middle ear anatomy such as extraordinarily inflated vestibules, lateroventrally orientated stapes with large footplates, and a small angle between the planes of the anterior and lateral semicircular canals. The vestibule has a volume, which is about 25 times larger than the human vestibule, although Kawingasaurus has only a skull length of approximately 40 mm. Vestibule inflation and enlarged stapes footplates are thought to be functionally correlated with bone‐conduction hearing; both morphologies have been observed in fossorial vertebrates using seismic signals for communication. The firmly fused triangular head with spatulate snout was probably used for digging and preadapted to seismic signal detection. The quadrate‐quadratojugal complex was able to transmit sound from the articular to the stapes by small vibrations of the quadrate process, which formed a ball and socket joint with the squamosal. Mechanical considerations suggest that the ventrolaterally orientated stapes of Kawingasaurus was mechanically better suited to transmit seismic sound from the ground to the fenestra vestibuli than a horizontal orientated stapes. The low sound pressure level transformer ratio of 2–3 in Kawingasaurus points to a seismic sensitivity of the middle ear and a vestigial or reduced sensitivity to airborne sound. Three hypothetical pathways of bone conduction in Kawingasaurus are discussed: 1) sound transmission via the spatulate snout and skull roof to the otic capsules, 2) relative movements resulting from the inertia of the mandible if sound is percepted with the skull, and 3) bone conduction from the substrate via mandible, jaw articulation, and stapes to the inner ear. J. Morphol. 276:121–143, 2015. © 2014 Wiley Periodicals, Inc.     

3D finite element model of the chinchilla ear for characterizing middle ear functions

Chinchilla is a commonly used animal model for research of sound transmission through the ear. Experimental measurements of the middle ear transfer function in chinchillas have shown that the middle ear cavity greatly affects the tympanic membrane (TM) and stapes footplate (FP) displacements. However, there is no finite element (FE) model of the chinchilla ear available in the literature to characterize the middle ear functions with the anatomical features of the chinchilla ear. This paper reports a recently completed 3D FE model of the chinchilla ear based on X-ray micro-computed tomography images of a chinchilla bulla. The model consisted of the ear canal, TM, middle ear ossicles and suspensory ligaments, and the middle ear cavity. Two boundary conditions of the middle ear cavity wall were simulated in the model as the rigid structure and the partially flexible surface, and the acoustic-mechanical coupled analysis was conducted with these two conditions to characterize the middle ear function. The model results were compared with experimental measurements reported in the literature including the TM and FP displacements and the middle ear input admittance in chinchilla ear. An application of this model was presented to identify the acoustic role of the middle ear septa—a unique feature of chinchilla middle ear cavity. This study provides the first 3D FE model of the chinchilla ear for characterizing the middle ear functions through the acoustic-mechanical coupled FE analysis.     

Formation of the middle ear: recent progress on the developmental and molecular mechanisms

The middle ear allows animals to hear while moving in an aerial medium. It is composed of a cavity harbouring a chain of three ossicles that transmit vibrations produced by airborne sound in the tympanic membrane into the inner ear, where they are converted into neural impulses. The middle ear develops in the branchial arches, and this requires sequential interactions between the epithelia and the underlying mesenchyme. Gene-inactivation experiments have identified genes required for the formation of different middle ear components. Some encode for signalling molecules, including Endothelin1 and Fgf8, probable mediators of epithelial-mesenchymal interactions. Other genes, including Eya1, Prx1, Hoxa1, Hoxa2, Dlx1, Dlx2, Dlx5, and Gsc, are most likely involved in patterning and morphogenetic processes in the neural crest-derived mesenchyme. Mechanisms controlling formation of a functional tympanic membrane are also discussed. Basically, the tympanic ring, which serves as support for the tympanic membrane, directs invagination of the first pharyngeal cleft ectoderm to form the external acoustic meatus (EAM), which provides the outer layer of the membrane. Gsc and Prx1 are essential for tympanic ring development. While invaginating, the EAM controls skeletogenesis in the underlying mesenchyme to form the manubrium of the malleus, the link between the membrane and the middle ear ossicles.     

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.     

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.     

Finite element analysis of the transfer of sound in the myringosclerotic ear

This work presents a biomechanical study of myringosclerosis (MS), an abnormal condition of the ear that produces calcification of the lamina propria of the eardrum. The study researched the transfer of sound to the stapes depending on the localization, dimension and calcification degree of the MS plaques. Results were obtained using a validated finite element model of the ear. The mechanical properties of the lamina propria were modified, in order to model MS plaques, using the rule of mixtures for particle composites considering that the plaques are made of hydroxyapatite particles in a matrix of connective tissue. Results show that the localization and dimension of the plaques are a factor of higher importance than calcification for loss of hearing through MS. The mobility of the stapes decreased with the presence of larger plaques and also when the tympanic annulus and the area of the handle of the malleus were involved.     

Ear ossicle morphology of the Jurassic euharamiyidan Arboroharamiya and evolution of mammalian middle ear

The middle ear bones of Mesozoic mammals are rarely preserved as fossils and the morphology of these ossicles in the earliest mammals remains poorly known. Here, we report the stapes and incus of the euharamiyidan Arboroharamiya from the lower Upper Jurassic (～160 Ma) of northern China, which represent the earliest known mammalian middle ear ossicles. Both bones are miniscule in relation to those in non‐mammalian cynodonts. The skull length/stapedial footplate diameter ratio is estimated as 51.74 and the stapes length as the percentage of the skull length is 4%; both numbers fall into the stapes size ranges of mammals. The stapes is “rod‐like” and has a large stapedial foramen. It is unique among mammaliaforms in having a distinct posterior process that is interpreted as for insertion of the stapedius muscle and homologized to the ossified proximal (stapedial) end of the interhyal, on which the stapedius muscle attached. The incus differs from the quadrate of non‐mammalian cynodonts such as morganucodontids in having small size and a slim short process. Along with lack of the postdentary trough and Meckelian groove on the medial surface of the dentary, the ossicles suggest development of the definitive mammalian middle ear (DMME) in Arboroharamiya. Among various higher‐level phylogenetic hypotheses of mammals, the one we preferred places “haramiyidans” within Mammalia. Given this phylogeny, development of the DMME took place once in the allotherian clade containing euharamiyidans and multituberculates, probably independent to those of monotremes and therians. Thus, the DMME has evolved at least three times independently in mammals. Alternative hypothesis that placed “haramiyidans” outside of Mammalia would require independent acquisition of the DMME in multituberculates and euharamiyidans as well as parallel evolution of numerous derived similarities in the dentition, occlusion pattern, mandibles, cranium, and postcranium between the two groups and between “haramiyidans” and other mammals. J. Morphol. 279:441–457, 2018. © 2016 Wiley Periodicals, Inc.     

Assembling a functional tympanic membrane: signals from the external acoustic meatus coordinate development of the malleal manubrium

In terrestrial mammals, hearing starts with the perception of acoustic pressure by the tympanic membrane. Vibrations in this membrane are then transduced into the inner ear by the ossicle chain of the middle ear, composed of the malleus, incus and stapes. The proper connection of the ossicle chain with the tympanic membrane, provided by the insertion of the manubrium of the malleus into the eardrum, is essential for the functionality of the hearing apparatus. We describe here the mechanisms regulating the development of the manubrium and its integration into the tympanic membrane. We show that the external acoustic meatus (EAM), which eventually forms the outer epithelium of the tympanic membrane, plays an essential role in this developmental process. Histological and expression analyses indicate that the manubrium develops close to the EAM with a similar temporal sequence. In addition, when the middle ear ossicles are allowed to develop in vitro under conditions that do not support further EAM development, the manubrium develops only up to the stage of its induction at the time of explantation. Moreover, genetically or teratogenically derived alterations in the EAM also have an effect on manubrial development. Finally, we show that the EAM is the source of two quite opposite activities, one that induces chondrogenesis and another that represses it. The combination of these two activities results in the proper positioning of the manubrium.     

A three-dimensional finite element model of round window membrane vibration before and after stapedotomy surgery

Piston stapes prostheses are implanted in patients with refractory conductive or mixed hearing loss due to stapes otosclerosis to stimulate the perilymph with varying degrees of success. The overclosure effect described by the majority of researchers affects mainly low and medium frequencies, and a large number of patients report a lack of satisfactory results for frequencies above 2 kHz. The mechanics of perilymph stimulation with the piston have not been studied in a systematic manner. The objective of this study was to assess the influence of stapedotomy surgery on round window membrane vibration and to estimate the postoperative outcomes using the finite element (FE) method. The study hypothesis is that the three-dimensional FE model developed of the human inner ear, which simulates the round window (RW) membrane vibration, can be used to assess the influence of stapedotomy on auditory outcomes achieved after the surgical procedure. An additional objective of the study was to enable the simulation of RW membrane vibration after stapedotomy using a new type of stapes prosthesis currently under investigation at Warsaw University of Technology. A three-dimensional finite element (FE) model of the human inner ear was developed and validated using experimental data. The model was then used to simulate the round window membrane vibration before and after stapedotomy surgery. Functional alterations of the RW membrane vibration were derived from the model and compared with the results of experimental measurements from temporal bones of a human cadaver. Piston stapes prosthesis implantation causes an approximately fivefold (14 dB) lower amplitude of the RW membrane vibrations compared with normal anatomical conditions. A satisfactory agreement between the FE model and the experimental data was found. The new prosthesis caused an increase of 20–30 dB in the RW displacement amplitude compared with the 0.4-mm piston prosthesis. In all frequencies, the FE model predicted a RW displacement curve that was above the experimental curves for the normal ear. The stapedotomy can be well simulated by the FE model to predict the auditory outcomes achieved following this otosurgery procedure. The 3D FE model developed in this study may be used to optimize the geometry of a new type of stapes prosthesis in order to achieve a similar sound transmission through the inner ear as for a normal middle ear. This should provide better auditory outcomes for patients with stapedial otosclerosis.     

The Codacs? Direct Acoustic Cochlear Implant Actuator: Exploring Alternative Stimulation Sites and Their Stimulation Efficiency

This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~ 5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5–141.8 eq. dB SPL; Omega/Aerial: 123.6–143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6–131.6 eq. dB SPL) and RW stimulation (108.3–128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~ 5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.     

Ontogenetic and phylogenetic transformations of the ear ossicles in marsupial mammals

This study is based on the examination of histological sections of specimens of different ages and of adult ossicles from macerated skulls representing a wide range of taxa and aims at addressing several issues concerning the evolution of the ear ossicles in marsupials. Three-dimensional reconstructions of the ear ossicles based on histological series were done for one or more stages of Monodelphis domestica, Caluromys philander, Sminthopsis virginiae, Trichosurus vulpecula, and Macropus rufogriseus. Several common trends were found. Portions of the ossicles that are phylogenetically older develop earlier than portions representing more recent evolutionary inventions (manubrium of the malleus, crus longum of the incus). The onset of endochondral ossification in the taxa in which this was examined followed the sequence; first malleus, then incus, and finally stapes. In M. domestica and C. philander at birth the yet precartilaginous ossicles form a supportive strut between the lower jaw and the braincase. The cartilage of Paauw develops relatively late in comparison with the ear ossicles and in close association to the tendon of the stapedial muscle. A feeble artery traverses the stapedial foramen of the stapes in the youngest stages of M. domestica, C. philander, and Sminthopsis virginiae examined. Presence of a large stapedial foramen is reconstructed in the groundplan of the Didelphidae and of Marsupialia. The stapedial foramen is absent in all adult caenolestids, dasyurids, Myrmecobius, Notoryctes, peramelids, vombatids, and phascolarctids. Pouch young of Perameles sp. and Dasyurus viverrinus show a bicrurate stapes with a sizeable stapedial foramen. Some didelphids examined to date show a double insertion of the Tensor tympani muscle. Some differences exist between M. domestica and C. philander in adult ossicle form, including the relative length of the incudal crus breve and of the stapes. Several differences exist between the malleus of didelphids and that of some phalangeriforms, the latter showing a short neck, absence of the lamina, and a ventrally directed manubrium. Hearing starts in M. domestica at an age in which the external auditory meatus has not yet fully developed, the ossicles are not fully ossified, and the middle ear space is partially filled with loose mesenchyme. The ontogenetic changes in hearing abilities in M. domestica between postnatal days 30 and 40 may be at least partially related to changes in middle ear structures.     

Auditory systems of Heteromyidae: functional morphology and evolution of the middle ear.

Middle ears (515) from 26 species of the rodent family Heteromyidae - genera Dipodomys, Microdipodops, Perognathus, and Liomys - were studied both grossly and histologically, for qualitative and quantitative comparisons. Middle ear modifications characteristic of each genus are qualitatively described. Quantitative comparisons are made among the 26 species in the study. Some correlations between middle ear size and other measurements are discussed. The middle ear is an acoustical transformer that for best efficiency must match the impedance of the cochlea to the impedance of the air in the external auditory meatus. It accomplishes this by a pressure increase and a velocity decrease through the combined effects of the lever and areal ratios; however, because the important consideration is a matching of two impedances rather than an absolute pressure increase, the pressure transformer ratio is a less informative measure of the middle ear's efficiency than is the impedance transform ratio. The impedance transformer mechanism is explained (from a morphological point of view), and equations are presented. Dipodomys, Microdipodops, and Perognathus have a theoretical transmission (at the resonant frequency) of 94-100% of the incident acoustical energy; Liomys, 78-80%. The areal ratio of stapes footplate to 2/3 tympanic membrane is remarkably constant among the species, varying only from 0.04 to 0.07: in Dipodomys and Microdipodops this small ratio is due to the very large tympanic membrane; in Perognathus and Liomys it is due to the extremely small stapes footplate. The lever ratio of incus to malleus varies from 0.28 to 0.33 in Dipodpmys and Microdipodops, from 0.37 to 0.46 in Perognathus, and from 0.55 to 0.60 in Liomys. In addition, the middle ear volumes and the morphology of tympanic membrane, ossicles, ligaments, and muscles, all combine to minimize both mass and stiffness. All these data suggest middle ear mechanisms which are very efficient over a broad frequency range. The middle ear modifications found in heteromyids are adaptive in predator avoidance, especially in areas of little natural cover; nevertheless, contrary to expectations, there is no firm relationship between habitat and the extent of these modifications in the 26 species. However, environment did apparently plan an important role in the evolution of the family, and this is discussed.     

The role of pressure difference reception in the directional hearing of budgerigars (Melopsittacus undulatus)

In many birds, the middle ears are connected through an air-filled interaural pathway. Sound transmission through this pathway may improve directional hearing. However, attempts to demonstrate such a mechanism have produced conflicting results. One reason is that some species of birds develop a lower static air pressure in the middle ears when anaesthetized, which reduces eardrum vibrations. In anaesthetized budgerigars with vented interaural air spaces and presumed normal eardrum vibrations, we find that sound propagating through the interaural pathway considerably improves cues to the directional hearing. The directional cues in the received sound combined with amplitude gain and time delay of sound propagating through the interaural pathway quantitatively account for the observed dependence of eardrum vibration on direction of sound incidence. Interaural sound propagation is responsible for most of the frontal gradient of eardrum vibration (i.e. when a sound source is moved from a small contralateral angle to the same ipsilateral angle). Our study confirms that at low frequencies the interaural sound propagation may cause vibrations of the eardrum to differ much in time, thus providing a possible cue for directional hearing. The acoustically effective size of the head of our birds (diameter 28 mm) is much larger than expected from the dimensions of the skull, so apparently the feathers on the head have a considerable acoustical effect.Dedicated to Professor Franz Huber on the occasion of his 80th birthday.     

Incudomalleal joint formation: the roles of apoptosis,migration and downregulation

Background  

The middle ear of mammals is composed of three endochondrial ossicles, the stapes, incus and malleus. Joints link the malleus to the incus and the incus to the stapes. In the mouse the first arch derived malleus and incus are formed from a single Sox9 and Type II collagen expressing condensation that later subdivides to give rise to two separate ossicles. In contrast the stapes forms from a separate condensation derived from the second branchial arch. Fusion of the malleus and incus is observed in a number of human syndromes and results in conductive hearing loss. Understanding how this joint forms during normal development is thus an important step in furthering our understanding of such defects.     

Fast Reverse Propagation of Sound in the Living Cochlea

The auditory sensory organ, the cochlea, not only detects but also generates sounds. Such sounds, otoacoustic emissions, are widely used for diagnosis of hearing disorders and to estimate cochlear nonlinearity. However, the fundamental question of how the otoacoustic emission exits the cochlea remains unanswered. In this study, emissions were provoked by two tones with a constant frequency ratio, and measured as vibrations at the basilar membrane and at the stapes, and as sound pressure in the ear canal. The propagation direction and delay of the emission were determined by measuring the phase difference between basilar membrane and stapes vibrations. These measurements show that cochlea-generated sound arrives at the stapes earlier than at the measured basilar membrane location. Data also show that basilar membrane vibration at the emission frequency is similar to that evoked by external tones. These results conflict with the backward-traveling-wave theory and suggest that at low and intermediate sound levels, the emission exits the cochlea predominantly through the cochlear fluids.     

Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution

The middle ear apparatus is composed of three endochondrial ossicles (the stapes, incus and malleus) and two membranous bones, the tympanic ring and the gonium, which act as structural components to anchor the ossicles to the skull. Except for the stapes, these skeletal elements are unique to mammals and are derived from the first and second branchial arches. We show that, in combination with goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine middle ear. During embryogenesis, Bapx1 is expressed in a discrete domain within the mandibular component of the first branchial arch and later in the primordia of middle ear-associated bones, the gonium and tympanic ring. Consistent with the expression pattern of Bapx1, mouse embryos deficient for Bapx1 lack a gonium and display hypoplasia of the anterior end of the tympanic ring. At E10.5, expression of Bapx1 partially overlaps that of Gsc and although Gsc is required for development of the entire tympanic ring, the role of Bapx1 is restricted to the specification of the gonium and the anterior tympanic ring. Thus, simple overlapping expression of these two genes appears to account for the patterning of the elements that compose the structural components of the middle ear and suggests that they act in concert. In addition, Bapx1 is expressed both within and surrounding the incus and the malleus. Examination of the malleus shows that the width, but not the length, of this ossicle is decreased in the mutant mice. In non-mammalian jawed vertebrates, the bones homologous to the mammalian middle ear ossicles compose the proximal jaw bones that form the jaw articulation (primary jaw joint). In fish, Bapx1 is responsible for the formation of the joint between the quadrate and articular (homologues of the malleus and incus, respectively) enabling an evolutionary comparison of the role of a regulatory gene in the transition of the proximal jawbones to middle ear ossicles. Contrary to expectations, murine Bapx1 does not affect the articulation of the malleus and incus. We show that this change in role of Bapx1 following the transition to the mammalian ossicle configuration is not due to a change in expression pattern but results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be essential in joint formation.     

The ear in subterranean insectivora and rodentia in comparison with ground-dwelling representatives. I. Sound conducting system of the middle ear.

Compared to acoustically unspecialized mammals (soricids and murids), the middle ear of subterranean insectivores and rodents (twelve species of six families examined) was clearly distinguished and characterized by many common features: rather round and relatively larger eardrum without a pars flaccida; reduced gonial; loose or no connection between the malleus and the tympanic bone; reduced and straightened transversal part of the malleus; enlarged incus; increased and rather flat incudo-mallear joint; rather parallel position of the mallear manubrium and incudal crus longum in some species (and their fusion in bathyergids); reduced or even missing middle ear muscles. Convergent occurrence of these structural features in taxa of different origin and their generally derived character suggest that they cannot be categorized as degenerative. The form of the stapes can be considered as a non-adaptive trait; it was taxon specific yet remarkably polymorphous in some species and exhibited no convergent features among subterranean mammals. Structural retrogression resulting in a columella-like stapes was observed in some species lacking the stapedial artery. The stapedial base was relatively larger than in unspecialized mammals. The subterranean mammals did not exhibit conspicuously enlarged eardrums as would be required for sensitive tuning to low frequencies. It is, however, argued that while selective pressures in the subterranean ecotope promoted hearing of low frequencies, hearing sensitivity did not have to be enhanced.