Assembling a functional tympanic membrane: signals from the external acoustic meatus coordinate development of the malleal manubrium.
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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. (+info)
Malleal processus brevis is dispensable for normal hearing in mice.
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The mammalian middle ear cavity contains a chain of three ossicles (the malleus, incus, and stapes), which develop from the mesenchyme of the first two branchial arches. Mice deficient in the Msx1 homeobox gene exhibit craniofacial abnormalities, including the absence of the malleal processus brevis that is normally attached to the upper part of the tympanic membrane. Here, we show that the expression of Msx1 and Msx2 overlaps in the malleal primordium during early embryonic development. A functional redundancy of Msx1 and Msx2 in the development of the middle ear is suggested by the stronger hypomorphism in the malleus of Msx1(-/-)/Msx2(-/-) embryos, including the absence of the malleal manubrium and the malleal processus brevis. The expression of Bmp4, a known downstream target of Msx1 in several developing craniofacial organs, was down-regulated in the malleal primordium, particularly in the region of the developing malleal manubrium, of Msx1 and Msx1(-/-)/Msx2(-/-) embryos. Msx genes, thus, appear to act in a cell autonomous manner, possibly by regulating Bmp4 expression, in the formation of the malleus. Transgenic rescue of the cleft palate of Msx1(-/-) mice overcame the neonatal lethality and allowed Msx1(-/-) mice to grow into adulthood but retain the phenotype of the absence of the malleal processus brevis. The availability of this animal model for the first time allowed us to measure auditory evoked potentials to assess the functional significance of the malleal processus brevis. The results demonstrated unimpaired auditory function in Msx1(-/-) mice. In addition, mutant mice appeared normal in balance behavior and in the vestibular evoked potential screening test. These results indicate that the malleal processus brevis is not necessary for sound transmission and seems dispensable for normal hearing and balance in mammals. (+info)
Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution.
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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. (+info)
Middle ear dynamics in response to seismic stimuli in the Cape golden mole (Chrysochloris asiatica).
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The hypertrophied malleus in the middle ear of some golden moles has been assumed to be an adaptation for sensing substrate vibrations by inertial bone conduction, but this has never been conclusively demonstrated. The Cape golden mole (Chrysochloris asiatica) exhibits this anatomical specialization, and the dynamic properties of its middle ear response to vibrations were the subjects of this study. Detailed three-dimensional middle ear anatomy was obtained by x-ray microcomputed tomography (muCT) at a resolution of 12 microm. The ossicular chain exhibits large malleus mass, selective reduction of stiffness and displacement of the center of mass from the suspension points, all favoring low-frequency tuning of the middle ear response. Orientation of the stapes relative to the ossicular chain and the structure of the stapes footplate enable transmission of substrate vibrations arriving from multiple directions to the inner ear. With the long axes of the mallei aligned parallel to the surface, the animal's head was stimulated by a vibration exciter in the vertical and lateral directions over a frequency range from 10 to 600 Hz. The ossicular chain was shown to respond to both vertical and lateral vibrations. Resonant frequencies were found between 71 and 200 Hz and did not differ significantly between the two stimulation directions. Below resonance, the ossicular chain moves in phase with the skull. Near resonance and above, the malleus moves at a significantly larger mean amplitude (5.8+/-2.8 dB) in response to lateral vs vertical stimuli and is 180 degrees out of phase with the skull in both cases. A concise summary of the propagation characteristics of both seismic body (P-waves) and surface (R-waves) is provided. Potential mechanisms by which the animal might exploit the differential response of the ossicular chain to vertical and lateral excitation are discussed in relation to the properties of surface seismic waves. (+info)
Joint formation in the middle ear: lessons from the mouse and guinea pig.
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The malleus, incus and stapes form an ossicle chain in the mammalian middle ear. These ossicles are articulated by joints that link the chain together. In humans and mice, fusion of the ossicles leads to hearing loss. However, in the adult guinea pig the malleus and incus are normally found as a single complex. In this report, we investigate how the malleus and incus form during mouse and guinea pig development. The murine malleus and incus develop from a single condensation that splits to form the two ossicles. Even before a morphological split, we show that the ossicles have distinct genetic identities and joint markers are expressed. In the guinea pig embryo, joint formation is initiated but no cavitation is observed, resulting in a single complex divided by a thin suture. The malleal-incudo complex in the guinea pig is, therefore, not caused by a defect in joint initiation. (+info)
Results after revision stapedectomy with malleus grip prosthesis.
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Revision stapedectomy with a malleus grip prosthesis is a technically challenging otologic procedure. The prosthesis is usually longer and extends deeper into the vestibule than a conventional stapes prosthesis, creating the potential to affect the vestibular sense organs. The prosthesis also bypasses the ossicular joints, which are thought to play a role in protecting the inner ear from large changes in static pressure within the middle ear. The prosthesis is in close proximity to the tympanic membrane, thus increasing the risk for its extrusion. We reviewed our experience with revision stapedectomy with the Schuknecht Teflon-wire malleus grip prosthesis in 36 ears with a mean follow-up of 23 months. The air-bone gap was closed to within 10 dB in 16 ears (44%) and to within 20 dB in 26 ears (72%). The incidence of postoperative sensorineural hearing loss was 8% (3 ears). There were no dead ears. Extrusion of the prosthesis occurred in 1 case (3%). Nearly 50% of patients reported various degrees of vertigo or disequilibrium during the first 3 weeks after surgery. These vestibular symptoms resolved by 6 weeks in all but 1 case. We did not find evidence of damage to the inner ear due to the length of the prosthesis or due to the potential for direct transmission of changes in static pressures within the middle ear to the labyrinth. Our results are similar to those published in the literature for malleus attachment stapedectomy and conventional revision incus stapedectomy. (+info)
Isolated fracture of the manubrium of the malleus.
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OBJECTIVE: To describe a series of five patients with isolated fracture of the manubrium of the malleus. DESIGN: Retrospective case series. SUBJECTS: Five patients aged 44-64 years with isolated fracture of the manubrium who presented to our institution over a five-year period (2000-2005). RESULTS: All patients presented with a history of digitally manipulating the external auditory canal, leading to the manubrial fracture, which we presume was due to a suction-type mechanism. Otomicroscopy often revealed a break in the smooth contour of the manubrium. All patients had air-bone gaps on audiometry, especially at higher frequencies. Tympanometry showed hypermobility of the tympanic membrane in four patients who were tested. Laser-Doppler vibrometry revealed increased umbo velocity in four out of five patients. Four patients were treated conservatively. One patient underwent exploratory tympanotomy with successful ossiculoplasty. CONCLUSIONS: Isolated fracture of the manubrium is a rare condition which may present as sudden-onset hearing loss after digital manipulation of the external auditory canal. The diagnosis can be made on the basis of otomicroscopy, audiometry, tympanometry and laser-Doppler vibrometry. Conservative treatment is often successful. (+info)
Clinical utility of laser-Doppler vibrometer measurements in live normal and pathologic human ears.
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The laser-Doppler vibrometer (LDV) is a research tool that can be used to quickly measure the sound-induced velocity of the tympanic membrane near the umbo (the inferior tip of the malleus) in live human subjects and patients. In this manuscript we demonstrate the LDV to be a sensitive and selective tool for the diagnosis and differentiation of various ossicular disorders in patients with intact tympanic membranes and aerated middle ears. Patients with partial or total ossicular interruption or malleus fixation are readily separated from normal-hearing subjects with the LDV. The combination of LDV measurements and air-bone gap can distinguish patients with fixed stapes from those with normal ears. LDV measurements can also help differentiate air-bone gaps produced by ossicular pathologies from those associated with pathologies of inner-ear sound conduction such as a superior semicircular canal dehiscence. (+info)