Hearing - Middle Ear Development

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Introduction

Adult hearing embryonic origins
Adult hearing embryonic origins.

The embryology of the middle ear requires many separate components from different embryonic origins. The tympanic membrane separates the outer ear from the middle ear and is formed initially from the first pharyngeal arch membrane. The middle ear bones (ossicles) are derived from separate origins in the first and second arch mesenchyme. The space in which these bones sit (tympanic cavity) is derived from the first pharyngeal pouch and is connected directly to the oral cavity by a hollow tube (auditory tube). In addition there are two muscles (tensor tympani and stapedius) formed from arch mesenchyme. (More? Pharyngeal Arches, Bone Development, Muscle Development).


Note that in other species, such as the guinea pig, the malleus and incus are normally found as a single complex.

Hearing Links: Introduction | Science Lecture | Medicine Lecture | Inner Ear | Middle Ear | Outer Ear | Balance | Hearing - Neural Pathway | Stage 22 | Abnormalities | Neonatal Diagnosis - Hearing | Hearing test | Sensory Introduction | Placodes | Student project | Category:Hearing
Historic Embryology 
Historic Embryology: 1902 Development of Hearing | 1906 Membranous Labyrinth | 1913 Tectorial Membrane | 1918 Human Embryo Otic Capsule | 1918 Cochlea | 1918 Grays Anatomy | 1922 Human Auricle | 1922 Otic Primordia | 1931 Internal Ear Scalae | 1933 Endolymphatic Sac | 1934 Otic Vesicle | 1934 Membranous Labyrinth | 1963 Human Otocyst | Historic Disclaimer

Some Recent Findings

  • A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw[1] "Multiple mammalian lineages independently evolved a definitive mammalian middle ear (DMME) through breakdown of Meckel's cartilage (MC). However, the cellular and molecular drivers of this evolutionary transition remain unknown for most mammal groups. Here, we identify such drivers in the living marsupial opossum Monodelphis domestica, whose MC transformation during development anatomically mirrors the evolutionary transformation observed in fossils. Specifically, we link increases in cellular apoptosis and TGF-BR2 signalling to MC breakdown in opossums. We demonstrate that a simple change in TGF-β signalling is sufficient to inhibit MC breakdown during opossum development, indicating that changes in TGF-β signalling might be key during mammalian evolution." TGF-beta
  • Early development of the malleus and incus in humans[2] "It is widely accepted by developmental biologists that the malleus and incus of the mammalian middle ear are first pharyngeal arch derivatives, a contention based originally on classical embryology that has now been backed up by molecular evidence from rodent models. However, it has been claimed in several studies of human ossicular development that the manubrium of the malleus and long process of the incus are actually derived from the second arch. This 'dual-arch' interpretation is commonly presented in otolaryngology textbooks, and it has been used by clinicians to explain the aetiology of certain congenital abnormalities of the human middle ear. In order to re-examine the origins of the human malleus and incus, we made three-dimensional reconstructions of the pharyngeal region of human embryos from 7 to 28 mm crown-rump length, based on serial histological sections from the Boyd Collection. ...We therefore conclude that the histological evidence, on balance, favours the 'classical' notion that the human malleus and incus are first-arch structures. The embryological basis of congenital ossicular abnormalities should be reconsidered in this light."
  • Fetal development of the elastic-fiber-mediated enthesis in the human middle ear[3] "In the human middle ear, the annular ligament of the incudostapedial joint and the insertions of the tensor tympani and stapedius muscles contain abundant elastic fibers; i.e., the elastic-fiber-mediated entheses. Hyaluronan also coexists with the elastic fibers. In the present study using immunohistochemistry, we demonstrated the distribution of elastin not only in the incudostapedial joint but also in the other two joints of the middle ear in adults and fetuses. In adults, the expression of elastin did not extend out of the annular ligament composed of mature elastic fibers but clearly overlapped with it. Electron microscopic observations of the annular ligament demonstrated a few microfibrils along the elastic fibers. Thus, in contrast to the vocal cord, the middle ear entheses seemed not to contain elaunin and oxytalan fibers. In mid-term fetuses (at approximately 15-16 weeks of gestation) before opening of the external acoustic meatus, the incudostapedial joint showed abundant elastic fibers, but the incudomalleolar and stapediovestibular joints did not. At this stage, hyaluronan was not colocalized, but distributed diffusely in loose mesenchymal tissues surrounding the ear ossicles. Therefore, fetal development of elastin and elastic fibers in the middle ear entheses is unlikely to require acoustic oscillation. In late-stage fetuses (25-30 weeks), whose ear ossicles were almost the same size as those in adults, we observed bundling and branching of elastic fibers. However, hyaluronan expression was not as strong as in adults. Colocalization between elastic fibers and hyaluronan appeared to be a result of postnatal maturation of the entheses."
  • Defects in middle ear cavitation cause conductive hearing loss in the Tcof1 mutant mouse[4] "Treacher Collins syndrome (TCS) is an autosomal dominant disorder of facial development that results from mutations in the gene TCOF1. CHL is a common feature of TCS but the causes of the hearing defect have not been studied. In this study, we have utilized Tcof1 mutant mice to dissect the developmental mechanisms underlying CHL. Our results demonstrate that effective cavitation of the middle ear is intimately linked to growth of the auditory bulla, the neural crest cell-derived structure that encapsulates all middle ear components, and that defects in these processes have a profoundly detrimental effect on hearing."
More recent papers  
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Search term: Middle Ear Development'

Oh Joon Kwon, Jae Moon Sung, Hwi Kyeong Jung, Chang Woo Kim Postoperative Mastoid Aeration Following Canal Wall Up Mastoidectomy according to Preoperative Middle Ear Disease: Analysis of Temporal Bone Computed Tomography Scans. J Audiol Otol: 2017, 21(3);140-145 PubMed 28942628

Neal Anthwal, Abigail S Tucker Q&A: Morphological insights into evolution. BMC Biol.: 2017, 15(1);83 PubMed 28915884

Neal Anthwal, Daniel J Urban, Zhe-Xi Luo, Karen E Sears, Abigail S Tucker Meckel's cartilage breakdown offers clues to mammalian middle ear evolution. Nat Ecol Evol: 2017, 1(4);93 PubMed 28812679

Toshiko Furutera, Masaki Takechi, Taro Kitazawa, Junko Takei, Takahiko Yamada, Tri Vu Hoang, Filippo M Rijli, Hiroki Kurihara, Shigeru Kuratani, Sachiko Iseki Differing contributions of the first and second pharyngeal arches to tympanic membrane formation in the mouse and chick. Development: 2017; PubMed 28807901


tensor tympani development José Francisco Rodríguez-Vázquez, Zhe Wu Jin, Peng Zhao, Gen Murakami, Xiang Wu Li, Yu Jin Development of digastric muscles in human fetuses: a review and findings in the flexor digitorum superficialis muscle. Folia Morphol. (Warsz): 2017; PubMed 28868605

Ana Sánchez-Del-Rey, José Maria Sánchez-Fernández, Arantza Ibargutxi, Agustin Martinez-Ibargüen, Francisco Santaolalla A comparative morphologic and morphometric study about geniculate ganglion development in man and in rat. Acta Otolaryngol.: 2016;1-9 PubMed 27910733

Jose Francisco Rodríguez-Vázquez, Yohei Honkura, Yukio Katori, Gen Murakami, Hiroshi Abe Fetal development of the pulley for muscle insertion tendons: A review and new findings related to the tensor tympani tendon. Ann. Anat.: 2016; PubMed 27693602

José Francisco Rodríguez-Vázquez, Koji Sakiyama, Hiroshi Abe, Osamu Amano, Gen Murakami Fetal tendinous connection between the tensor tympani and tensor veli palatini muscles: A single digastric muscle acting for morphogenesis of the cranial base. Anat Rec (Hoboken): 2016; PubMed 26744237

A Blanke, H Aupperle, J Seeger, C Kubick, G F Schusser Histological Study of the External, Middle and Inner Ear of Horses. Anat Histol Embryol: 2014; PubMed 25283481


stapedius development

Middle Ear Origins

Pharyngeal arch cartilages
  • neural crest from the first and second pharyngeal arches forms the cartilage origin of the middle ear bones (ossicles).
    • first arch cartilage - (Meckel's) malleus and incus
    • second arch cartilage - (Reichart's) stapes
  • first pharyngeal pouch endoderm forms the auditory tube that enlarges to incorporate the tympanic cavity surrounding the ossicles.
    • endoderm forms the lining epithelium and glands.
  • mesoderm from the first and second arch forms the middle ear muscles
    • first arch - tensor tympani muscle
    • second arch - stapedius muscle

Middle Ear Genes - gooscoid, RARs, Prx1, Otx2, Hoxa1, Hoxb1, endothelian related molecules

Eustacian tube angle

Week 8

Cross-section of human embryo Carnegie stage 22 during Week 8.

Stage 22 image 159.jpg Stage 22 image 161.jpg

Middle ear structure visible are the primordial maleus, the developing tensor tympani muscle, the developing auditory tube (tubo tympanic recess) extending from the oral cavity towards the middle ear region. Note the ossicle is still embedded, and surrounded by, the mesenchyme of the head.

Ossicles

Gray0916.jpg Gray0917.jpg Gray0918.jpg
Malleus
Incus
Stapes

Middle ear development begins closely associated with head formation and involves both the foregut tube (pharynx) and the pharyngeal arches. Pharyngeal arches form the main anatomical structures of the head and neck, including all components of the middle and outer ear.

The three middle ear bones or auditory ossicles (malleus, incus, stapes) are formed from the cartilage template found within pharyngeal arch 1 and 2. These bones are commonly named the hammer (malleus), anvil (incus) and stirrup (stapes), and the cartilage bands are historically named after two German anatomists and are called Meckel’s cartilage (first pharyngeal arch; named after Johann Friedrich Meckel, 1781–1833) and Reichert’s cartilage (second pharyngeal arch; named after Karl Bogislaus Reichert, 1811–1883). There are several theories as to how each arch cartilage contributes individual components of the middle ear ossicles. For example, a recent study suggests a mesenchymal origin for the stapes rather than directly from Reichert's cartilage.[5] Meckel’s cartilage first appears histologically at Carnegie stage 16 and Reichert’s cartilage slightly later.

The early stages of auditory ossicle development all occur within the solid mesenchyme of the pharyngeal arches until the eighth month of development, then within a fluid-filled space for the final month, and finally only postnatal in the neonate in the air-filled tympanic cavity. This transition in auditory ossicle environment means that the middle ear does not function correctly until after birth, and any prenatal conduction to the cochlea must be mediated through bone conduction.

During development of the tympanic cavity, the auditory ossicles are held in their correct anatomic positions by supporting ligaments. Arch cartilages ossify by the process of endochondral ossification, where a pre-existing cartilage template is first formed and later replaced by bone. Endochondral ossification is the main process of bone formation throughout the entire skeleton, except for the cranial vault and the clavicle that ossify by a process of intramembranous ossification.

Initially, the malleus and incus form as a single structure, and it is only later that they separate to form two separate bones. Ossification continues through the entire fetal period, and the newly formed bones also have a transient bone marrow cavity. The marrow cavity is still present at birth, in both the malleus and the incus, and with continued ossification is lost during the first two years after birth. Postnatally, first the malleus and then the incus lose their marrow spaces.

Malleus

Gray0916.jpg

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

This ossicle 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.[6][7]

The newborn and infant malleus head normally contains bone marrow, that is eventually replaced by bone.[8]

Malleus Development (timing from [7])

  • 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
Adult Malleus Anatomy
Component Description
Head (capitulum mallei) large upper extremity of the bone, oval in shape articulates posteriorly with the incus, being free in the rest of its extent facet for articulation with the incus is constricted near the middle (consists of an upper larger and lower smaller part nearly a right angle with each other) opposite the constriction (lower margin of the facet projects in the form of a process, cog-tooth or malleus spur)
Neck (collum mallei) narrow contracted part, just beneath the head below it is a prominence various processes are attached to the prominence
Handle (manubrium mallei) connected by its lateral margin with the tympanic membrane directed downward, medialward, and backward decreases in size toward its free end, which is curved slightly forward, and flattened transversely. Medial side, near its upper end, is a slight projection, into which the tendon of the tensor tympani is inserted
Anterior Process (processus anterior (Folii), processus gracilis) delicate spicule from the eminence below the neck directed forward to the petrotympanic fissure to which it is connected by ligamentous fibers
Lateral Process (processus lateralis, processus brevis) a slight conical projection from the root of the manubrium directed laterally, and is attached to the upper part of the tympanic membrane attached by means of the anterior and posterior malleolar folds, to the extremities of the notch of Rivinus.
(some text modified from Gray's Anatomy)

Incus

Gray0917.jpg

Incus (left) A. From within. B. From the front

Originally named from resemblance to an anvil, onsists of a body and two crura.

The two crura diverge from one another nearly at right angles.

Gray suggested the incus has more like a "premolar tooth" appearance, with two roots, which differ in length, and are widely separated from each other.

Incus ossification is initiated in the fetal period.[6]

Incus Development (timing from [7])

  • 16 weeks - force lines start through two cortical fascicles in the long process
  • 17 to 20 weeks - two cortical fascicles progressively extend in a rostro-caudal direction
  • 21 weeks - occupy the whole extension of the long process
  • 22 weeks - fusion of both cortical fascicles begins.
  • 30 weeks - strengthened by the crossing of bone trabeculae from one cortical to another. Two fascicles come out of the incus body, surrounding the medullary cavity and going in the direction of the short process.

The newborn and infant incus body normally contains bone marrow, that is eventually replaced by bone.[8]

Adult Incus Anatomy
Component Description
Body (corpus incudis) somewhat cubical but compressed transversely anterior surface is a deeply concavo-convex facet facet articulates with the head of the malleus
Short Crus (crus breve, short process) somewhat conical in shape projects almost horizontally backward attached to the fossa incudis, in the lower and back part of the epitympanic recess
Long Crus (crus longum, long process) descends nearly vertically behind and parallel to the manubrium of the malleus bending medialward, ends in a rounded projection, the lenticular process lenticular process is tipped with cartilage, and articulates with the head of the stapes

Stapes

Gray0918.jpg

A. Left stapes. B. Base of stapes, medial surface.

Originally named by its resemblance to a stirrup and structurally consists of a head, neck, two crura, and a base.

Stapes Development (timing from [7])

  • 28 weeks - tympanic membrane of the stapes footplate undergoes a remodelling process with bony trabeculae deposited
Adult Stapes Anatomy
Component Description
Head (capitulum stapedis) presents a depression, which is covered by cartilage articulates with the lenticular process of the incus
Neck constricted part of the bone, succeeding the head gives insertion to the tendon of the Stapedius muscle
Two crura (crus anterius and crus posterius) diverge from the neck , connected at their ends by a flattened oval plate anterior is shorter and less curved than the posterior
Base (basis stapedis) forms the foot-plate of the stirrup fixed to the margin of the fenestra vestibuli by a ring of ligamentous fibers

Tympanic Membrane

The tympanic membrane (membrana tympani) or "ear drum", separates the external acoustic meatus from the tympanic cavity. In the adult, this thin membrane is nearly oval in shape about 9 to 10 mm in diameter. The circumference is slightly thickened to form a fibrocartilaginous ring that is attached to the tympanic sulcus at the inner end of the meatus. The malleus manubrium is attached to the medial surface of the membrane and is the mechanism for transmitting vibration of the tympanic membrane to the other middle ear ossicles. See also recent review.[9]

Middle Ear Muscles

Tensor tympani development, week 8 stage 22

The middle ear also contains the two smallest muscles of the body, the stapedius and tensor tympani muscles, which both differentiate from arch mesenchyme. These muscles form and differentiate in a similar fashion to other developing skeletal muscle. Initially myoblasts proliferate under the influence of growth factors in the region of where the muscle will form. Myoblasts are the embryonic undifferentiated single cells of all skeletal muscles.

  • The adult tensor tympani is classed as a mixed muscle containing slow (type 1) and fast (type 2A, and probably 2X) muscle fibers.
  • The adult mammalian stapedius muscle contains mainly (77%) fast oxidative glycolytic type muscle fibers and the avian muscle only contains fast fibers.

A recent study[10] of the stapedius region (see table below) and muscle development in 50 human embryos and fetuses between 38 days to 17 weeks post-conception identified 2 origins:

  1. for the tendon - derives from the internal segment of the interhyale
  2. for the belly - located in the second pharyngeal arch, medially to the facial nerve and near the interhyale

interhyale - term describing the internal part of the second pharyngeal arch that forms the tendon of the stapedius muscle

Carnegie Stage CRL (mm) Description
13 6 Presumptive stapedial area
14 7 Appearance of the stapedial anlage
16 9 Relationship between the stapedial artery and the stapedial anlage. Appearance of the interhyale
17 12 Delimitation of the parts of the stapedial anlage
18 16 Chondrogenesis phase. Start of involution of the stapedial artery
20 18.5 Delimitation of the ossicular anlages. Cartilaginous phase. Disappearance of the stapedial artery
22 26 Delimitation of the interhyale
23 28 Anlage of the stapedial muscle tendon
Data summarised from Table 1[10]
Links: Musculoskeletal System - Muscle Development

Tympanic Cavity

The tympanic cavity (cavum tympani) extends from the first pharyngeal pouch to surround the middle ear ossicles. This small air-filled space is connected to the oral cavity by the narrow auditory tube. The adult tympanic cavity anatomy is a single space constricted slightly into an upper (attic) and a lower (atrium) chamber.

Auditory Tube

The auditory tube or eustachian tube (named after Bartolomeo Eustachi, 1500–1574) (or otopharyngeal or pharyngotympanic tube) develops from the first pharyngeal pouch and is lined with endoderm. This narrow cavity links the pharynx to the middle ear and is continuous with the tympanic cavity. The auditory tube has two main functions: ventilation, to allow the equalization of pressure in the middle ear, and clearance, to allow the middle ear fluid continuously produced by the epithelial lining to drain from the middle ear.

In normal human development, the auditory tube has an almost straight posterolateral to anteromedial pathway. The main growth of the auditory tube occurs in extension and lumen of the cartilaginous portion in the fetal period between weeks 16 to 28.

At birth, and in the young child, the tube is both shorter (8-9 mm) compared
to the adult length (17-18 mm), runs almost horizontal and is narrower in
diameter. Head growth in the child to adult size results in a longer wider tube that runs at approximately 45 degrees to the horizontal. The auditory tube is also normally closed and is opened by muscles—in the infant this is only a single muscle, the tensor palati muscle. In the adult the auditory tube is now opened by two separate muscles, the tensor palati and levator palati muscles.

he middle ear cavity or tympanic cavity is formed by an expansion of the pharynx. The initial early cavity lining is formed by the pharyngeal endoderm epithelium. The epithelium will then continue to expand, to eventually also line the entire mastoid antrum.

  • derived from first pharyngeal pouch
  • extends as tubotympanic recess - during week 5 recess contacts outer ear canal
  • mesoderm between 2 canals forms tympanic membrane
  • expands to form tympanic recess
  • stalk of recess forms auditory tube(eustachian tube, pharyngotympanic tube)

Auditory Tube Postnatal Changes

Eustacian tube angle.jpg

Adult

  • longer (34-36 mm)
  • wider
  • runs at approximately 45 degrees to the horizontal
  • opened by two separate muscles (tensor palati and levator palati)



Birth

  • shorter (17-18 mm)
  • narrower
  • runs almost horizontal
  • opened by a single muscle (tensor palati muscle)

Adult Middle Ear

The adult middle ear, like the inner ear, eventually will lie within the petrous portion of temporal bone. Initially, both the middle and inner ear form within mesenchyme, embryonic connective tissue, forming the otic capsule, and this will also form the base of the skull. The mesenchyme differentiates first to form cartilage, forming a structure known as the chondrocranium. This initial cartilage is gradually replaced by bone forming at a number of sites within the cartilage, ossification centers. The initial bone that is formed also contains marrow spaces that disappear with ongoing ossification (Yokoyama et al., 1999). Between the weeks 16 to 24, centers of ossification appear in the remaining cartilage of the otic capsule, and these continue to ossify to eventually form mastoid process of temporal bone.


Other Species

Avian - the columella is a single ossicle, it has a shaft and footplate inserted into the oval window.

Additional Images

Historic

Historic Disclaimer - information about historic embryology pages 
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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Keith A. Human Embryology and Morphology. (1902) London: Edward Arnold.

Frazer JE. The early formations of the middle ear and eustachian tube - a criticism. (1922) J Anat. 57(1): 18-30. PMID 17103958

References

  1. Daniel J Urban, Neal Anthwal, Zhe-Xi Luo, Jennifer A Maier, Alexa Sadier, Abigail S Tucker, Karen E Sears A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw. Proc. Biol. Sci.: 2017, 284(1848); PubMed 28179517
  2. Charlotte M Burford, Matthew J Mason Early development of the malleus and incus in humans. J. Anat.: 2016; PubMed 27456698
  3. Yoshitaka Takanashi, Shunichi Shibata, Yukio Katori, Gen Murakami, Shinichi Abe, Jose Francisco Rodríguez-Vázquez, Tetsuaki Kawase Fetal development of the elastic-fiber-mediated enthesis in the human middle ear. Ann. Anat.: 2013, 195(5);441-8 PubMed 23706648
  4. Carol A Richter, Susan Amin, Jennifer Linden, Jill Dixon, Michael J Dixon, Abigail S Tucker Defects in middle ear cavitation cause conductive hearing loss in the Tcof1 mutant mouse. Hum. Mol. Genet.: 2010, 19(8);1551-60 PubMed 20106873
  5. J F Rodríguez-Vázquez Development of the stapes and associated structures in human embryos. J. Anat.: 2005, 207(2);165-73 PubMed 16050903
  6. 6.0 6.1 J M Sánchez-Fernández, S Saint-Gerons, A Sánchez del Rey A microanalytical study on human auditory ossicles in normal and pathological conditions. Acta Otolaryngol.: 1992, 112(2);317-21 PubMed 1604999
  7. 7.0 7.1 7.2 7.3 J Whyte, A Cisneros, C Yus, J Obón, A Whyte, P Serrano, C Pérez-Castejón, A Vera Development of the dynamic structure (force lines) of the middle ear ossicles in human foetuses. Histol. Histopathol.: 2008, 23(9);1049-60 PubMed 18581276
  8. 8.0 8.1 T Yokoyama, Y Iino, K Kakizaki, Y Murakami Human temporal bone study on the postnatal ossification process of auditory ossicles. Laryngoscope: 1999, 109(6);927-30 PubMed 10369284
  9. Masaki Takechi, Taro Kitazawa, Tatsuya Hirasawa, Tamami Hirai, Sachiko Iseki, Hiroki Kurihara, Shigeru Kuratani Developmental mechanisms of the tympanic membrane in mammals and non-mammalian amniotes. Congenit Anom (Kyoto): 2016, 56(1);12-7 PubMed 26754466
  10. 10.0 10.1 J F Rodríguez-Vázquez, J R Mérida-Velasco, S Verdugo-López Development of the stapedius muscle and unilateral agenesia of the tendon of the stapedius muscle in a human fetus. Anat Rec (Hoboken): 2010, 293(1);25-31 PubMed 19899117


Reviews

Masaki Takechi, Taro Kitazawa, Tatsuya Hirasawa, Tamami Hirai, Sachiko Iseki, Hiroki Kurihara, Shigeru Kuratani Developmental mechanisms of the tympanic membrane in mammals and non-mammalian amniotes. Congenit Anom (Kyoto): 2016, 56(1);12-7 PubMed 26754466

Susan Caroline Chapman Can you hear me now? Understanding vertebrate middle ear development. Front Biosci (Landmark Ed): 2011, 16;1675-92 PubMed 21196256

| PMC3065862 Masaki Takechi, Shigeru Kuratani History of studies on mammalian middle ear evolution: a comparative morphological and developmental biology perspective. J. Exp. Zool. B Mol. Dev. Evol.: 2010, 314(6);417-33 PubMed 20700887


Articles

Alison S Laufer, Joshua P Metlay, Janneane F Gent, Kristopher P Fennie, Yong Kong, Melinda M Pettigrew Microbial communities of the upper respiratory tract and otitis media in children. MBio: 2011, 2(1);e00245-10 PubMed 21285435

J F Rodríguez-Vázquez Development of the stapes and associated structures in human embryos. J. Anat.: 2005, 207(2);165-73 PubMed 16050903


Search PubMed

May 2010 "Middle Ear Development" All (2368) Review (226) Free Full Text (272)


Search Pubmed: Middle Ear Development | Ossicle Development | Malleus Development | Incus Development | Stapes Development | Tympanic Membrane Development

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Cite this page: Hill, M.A. 2017 Embryology Hearing - Middle Ear Development. Retrieved September 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Hearing_-_Middle_Ear_Development

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