Difference between revisions of "Talk:Hearing - Middle Ear Development"

From Embryology
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Bone morphogenetic protein 4; Conductive hearing loss; Endoderm; Middle ear; Mouse; Neural crest; Ossicles; Sonic hedgehog
Bone morphogenetic protein 4; Conductive hearing loss; Endoderm; Middle ear; Mouse; Neural crest; Ossicles; Sonic hedgehog
PMID: 30630826 DOI: 10.1242/dev.167965
PMID: 30630826 DOI: 10.1242/dev.167965
===Pars tensa and tympanicomalleal joint: proposal for a new anatomic classification===
===Pars tensa and tympanicomalleal joint: proposal for a new anatomic classification===

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Cite this page: Hill, M.A. (2021, May 11) Embryology Hearing - Middle Ear Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Hearing_-_Middle_Ear_Development

guinea pig the malleus and incus are normally found as a single complex


Region-specific endodermal signals direct neural crest cells to form the three middle ear ossicles

Development. 2019 Jan 22;146(2). pii: dev167965. doi: 10.1242/dev.167965.

Ankamreddy H1,2, Min H1, Kim JY1,2, Yang X3, Cho ES4, Kim UK5,6, Bok J7,2,8.

Defects in the middle ear ossicles - malleus, incus and stapes - can lead to conductive hearing loss. During development, neural crest cells (NCCs) migrate from the dorsal hindbrain to specific locations in pharyngeal arch (PA) 1 and 2, to form the malleus-incus and stapes, respectively. It is unclear how migratory NCCs reach their proper destination in the PA and initiate mesenchymal condensation to form specific ossicles. We show that secreted molecules sonic hedgehog (SHH) and bone morphogenetic protein 4 (BMP4) emanating from the pharyngeal endoderm are important in instructing region-specific NCC condensation to form malleus-incus and stapes, respectively, in mouse. Tissue-specific knockout of Shh in the pharyngeal endoderm or Smo (a transducer of SHH signaling) in NCCs causes the loss of malleus-incus condensation in PA1 but only affects the maintenance of stapes condensation in PA2. By contrast, knockout of Bmp4 in the pharyngeal endoderm or Smad4 (a transducer of TGFβ/BMP signaling) in the NCCs disrupts NCC migration into the stapes region in PA2, affecting stapes formation. These results indicate that region-specific endodermal signals direct formation of specific middle ear ossicles. © 2019. Published by The Company of Biologists Ltd. KEYWORDS: Bone morphogenetic protein 4; Conductive hearing loss; Endoderm; Middle ear; Mouse; Neural crest; Ossicles; Sonic hedgehog PMID: 30630826 DOI: 10.1242/dev.167965


Pars tensa and tympanicomalleal joint: proposal for a new anatomic classification

Eur Arch Otorhinolaryngol. 2019 Aug;276(8):2141-2148. doi: 10.1007/s00405-019-05434-4. Epub 2019 Apr 19.

Gilberto N1,2,3, Santos R4, Sousa P4, O'Neill A4,5, Escada P4, Pais D5.

PURPOSE: The tympanic membrane (TM) belongs to the ear. Despite its place in the ear anatomy, can we give it also a different anatomic classification? The main objective is to clarify the nature of TM, tympanic bone and malleus to propose a new anatomic classification. METHODS: This cadaveric study was performed in two human heads and six fresh temporal bones. A study of the temporomandibular joint, external acoustic meatus (EAM), TM and middle ear structures was conducted. A medical literature review englobing anatomy, embryology, histology and phylogeny of the ear was performed and the results were compared with the results of the dissection. RESULTS: The external ear is constituted by the auricle and the EAM. This last segment is made by a cartilaginous and an osseous portion. The osseous portion of the EAM is constituted mainly by tympanic bone. The external ear is separated from the middle ear by the TM. Inside the middle ear, there are three ossicles: malleus, incus and stapes, which allow the conduction of sound to the cochlea. Based on the anatomic dissection and medical literature review of the tympanic bone, malleus and TM, we propose that these structures are interconnected like a joint, and named it "Tympanicomalleal joint". CONCLUSIONS: It seems that the TM can be part of a joint that evolved to improve sound transmission and middle ear protection. Thinking TM has part of a joint may help in the development of more efficient reconstructive surgical techniques. KEYWORDS: Anatomy; Ear ossicles; External ear; Middle ear; Tympanic membrane; Tympanoplasty PMID: 31004197 DOI: 10.1007/s00405-019-05434-4


Reporting and Description for Congenital Middle Ear Malformations to Facilitate Surgical Management

Ann Otol Rhinol Laryngol. 2018 Oct;127(10):717-725. doi: 10.1177/0003489418792939. Epub 2018 Aug 9.

Yang F1, Liu Y2.


INTRODUCTION: The aim of this work was to report and describe the different types of congenital middle ear malformations in order to guide surgical treatment approaches and improve outcomes for affected patients. METHODS: The authors reviewed patients with congenital middle ear malformations who received surgical treatment between September 2010 and March 2017. Patient characteristics, middle ear deformities, and surgical procedures were documented. RESULTS: In this retrospective study, 35 patients were reviewed. A description of middle ear malformation was proposed that considers ear embryogenesis and focuses on stapes deformity, with the main purpose of facilitating surgical approach selection to reconstruct the ossicular chain. Patients were classified into 3 categories: type I (19 cases), mobile stapes footplate, which included type Ia with normal stapes suprastructure and type Ib with abnormal stapes suprastructure; type II (4 cases), fixed stapes footplate, which included type IIa with normal ossicular chain and type IIb with abnormal ossicular chain; and type III (12 cases), oval window bony atresia or aplasia, with or without round window atresia. Types II and III could have concomitant aberrant facial nerve. Different surgical approaches are described. CONCLUSIONS: The authors describe the different types of congenital middle ear malformations. This category description considers ear embryogenesis and is focused on stapes deformity. It may provide better understanding of disease development and guide modern hearing reconstructive surgery. KEYWORDS: classification; congenital malformations; middle ear; surgical treatment PMID: 30091369 DOI: 10.1177/0003489418792939

Hox-A2 protein expression in mouse embryo middle ear ossicles

Morphologie. 2018 Sep 26. pii: S1286-0115(18)30190-5. doi: 10.1016/j.morpho.2018.09.002. [Epub ahead of print]

Louryan S1, Lejong M2, Choa-Duterre M2, Vanmuylder N2.


The origin of the mammalian middle ear ossicles from mandibular and hyoid pharyngeal arches remains controversial and discussed. Two adverse theories are proposed. The first claims that malleus and incus derive from the Meckel's cartilage of the mandibular arch, and stapes from Reichert's cartilage of the hyoid arch. The second postulates that handle of malleus and long process of the incus are derived from the second arch as well as the stapes. Contradictory analyses support alternatively each theory without any experimental evidence. In order to bring new data, we analyzed by immunohistochemistry the expression of Hox-A2 protein in ossicular anlagen in E11 to 13 mouse embryos. HOXA2 gene is known to be expressed in second arch cells and to be absent from mandibular arch derivatives. Surprisingly, Hox-A2 protein was present in all ossicular primordia, as well in Reichert's cartilage. Meckel's cartilage was free of staining. Unlabeled cells were also present in ossicular blastemata. These results suggest that ossicular condensations could arise from mixed cell populations originated in both mandibular and hyoid pharyngeal arches. However, we cannot exclude that diffuse Hox-A2 immunoreactivity could correspond to a secondary expression in craniofacial mesenchyme independently from the branchial origin of cells. KEYWORDS: Embryo; Hoxa-2; Mouse; Ossicles; Pharyngeal arches PMID: 30268353 DOI: 10.1016/j.morpho.2018.09.002

Development of the Human Incus With Special Reference to the Detachment From the Chondrocranium to be Transferred into the Middle Ear

Anat Rec (Hoboken). 2018 Apr 18. doi: 10.1002/ar.23832. [Epub ahead of print]

Rodríguez-Vázquez JF1, Yamamoto M2, Abe S2, Katori Y3, Murakami G4.


The mammalian middle ear represents one of the most fundamental features defining this class of vertebrates. However, the origin and the developmental process of the incus in the human remains controversial. The present study seeks to demonstrate all the steps of development and integration of the incus within the middle ear. We examined histological sections of 55 human embryos and fetuses at 6 to 13 weeks of development. At 6 weeks of development (16 Carnegie Stage), the incus anlage was found at the cranial end of the first pharyngeal arch. At this stage, each of the three anlagen of the ossicles in the middle ear were independent in different locations. At Carnegie Stage 17 a homogeneous interzone clearly defined the incus and malleus anlagen. The cranial end of the incus was located very close to the otic capsule. At 7 and 8 weeks was characterized by the short limb of the incus connecting with the otic capsule. At 9 weeks was characterized by an initial disconnection of the incus from the otic capsule. At 13 weeks, a cavity appeared between the otic capsule and incus. Our results provide significant evidence that the human incus developed from the first pharyngeal arch but independently from Meckel's cartilage. Also, during development, the incus was connected with the otic capsule, and then it was detached definitively. The development of the incus in humans provides evidence that this ossicle is homologous to the quadrate. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. KEYWORDS: auditory ossicles; human embryology; incus; middle ear; quadrate PMID: 29669196 DOI: 10.1002/ar.23832

Incus Timeline

  • Week 6
    • Carnegie Stage 16) incus anlage was found at the cranial end of the first pharyngeal arch.
    • Carnegie Stage {{CS17}) a homogeneous interzone clearly defined the incus and malleus anlagen. The cranial end of the incus was located very close to the otic capsule.
  • Week 7 and 8 - short limb of the incus connecting with the otic capsule.
  • Week 9 - an initial disconnection of the incus from the otic capsule.
  • Week 13 - a cavity appeared between the otic capsule and incus.


A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw

Proc Biol Sci. 2017 Feb 8;284(1848). pii: 20162416. doi: 10.1098/rspb.2016.2416.

Urban DJ1, Anthwal N2, Luo ZX3, Maier JA1, Sadier A1, Tucker AS2, Sears KE4,5.


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. Furthermore, the apoptosis that we observe during opossum MC breakdown does not seemingly occur in mouse, consistent with homoplastic DMME evolution in the marsupial and placental lineages. © 2017 The Author(s). KEYWORDS: Meckel's cartilage; TGFB signalling; apoptosis; marsupial; origin of mammals

PMID 28179517 DOI: 10.1098/rspb.2016.2416


Early development of the malleus and incus in humans

J Anat. 2016 Dec;229(6):857-870. doi: 10.1111/joa.12520. Epub 2016 Jul 26.

Burford CM1, Mason MJ1.


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 considered the positions of the developing ossicles relative to the pharyngeal pouches and clefts, and the facial and chorda tympani nerves. Confirming observations from previous studies, the primary union between first pharyngeal pouch and first cleft found in our youngest specimens was later lost, the external meatus developing rostroventral to this position. The mesenchyme of the first and second arches in these early embryos seemed to be continuous, but the boundaries of the developing ossicles proved to be very hard to determine at this stage. When first distinguishable, the indications were that both the manubrium of the malleus and the long process of the incus were emerging within the first pharyngeal arch. 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. © 2016 Anatomical Society. KEYWORDS: development; embryology; incus; malleus; pharyngeal arch PMID 27456698 DOI: 10.1111/joa.12520

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 Jan 6. doi: 10.1002/ar.23310. [Epub ahead of print]

Rodríguez-Vázquez JF1, Sakiyama K2, Abe H3, Amano O2, Murakami G4.


Some researchers contend that in adults the tensor tympani muscle (TT) connects with the tensor veli palatini muscle (TVP) by an intermediate tendon, in disagreement with the other researchers. To resolve this controversy, we examined serial sections of 50 human embryos and fetuses at 6-17 weeks of development. At 6 weeks, in the first pharyngeal arch, a mesenchymal connection was found first to divide a single anlage into the TT and TVP. At and after 7 weeks, the TT was connected continuously with the TVP by a definite tendinous tissue mediolaterally crossing the pharyngotympanic tube. At 11 weeks another fascia was visible covering the cranial and lateral sides of the tube. This "gonial fascia" had two thickened borders: the superior one corresponded to a part of the connecting tendon between the TT and TVP; the inferior one was a fibrous band ending at the os goniale near the lateral end of the TVP. In association with the gonial fascia, the fetal TT and TVP seemed to provide a functional complex. The TT-TVP complex might first help elevate the palatal shelves in association with the developing tongue. Next, the tubal passage, maintained by contraction of the muscle complex, seems to facilitate the removal of loose mesenchymal tissues from the tympanic cavity. Third, the muscle complex most likely determined the final morphology of the pterygoid process. Consequently, despite the controversial morphologies in adults, the TT and TVP seemed to make a single digastric muscle acting for the morphogenesis of the cranial base. This article is protected by copyright. All rights reserved. © 2016 Wiley Periodicals, Inc. KEYWORDS: middle ear; palatal shelves; pharyngotympanic tube; tensor tympani muscle; tensor veli palatini muscle

PMID 26744237


Developmental origin and fate of middle ear structures

Hear Res. 2013 Jul;301:19-26. doi: 10.1016/j.heares.2013.01.019. Epub 2013 Feb 8.

Sienknecht UJ1.


Results from developmental and phylogenetic studies have converged to facilitate insight into two important steps in vertebrate evolution: (1) the ontogenetic origin of articulating elements of the buccal skeleton, i.e., jaws, and (2) the later origins of middle ear impedance-matching systems that convey air-borne sound to the inner ear fluids. Middle ear ossicles and other skeletal elements of the viscerocranium (i.e., gill suspensory arches and jaw bones) share a common origin both phylogenetically and ontogenetically. The intention of this brief overview of middle-ear development is to emphasize the intimate connection between evolution and embryogenesis. Examples of developmental situations are discussed in which cells of different provenance, such as neural crest, mesoderm or endoderm, gather together and reciprocal interactions finally determine cell fate. Effects of targeted mutagenesis on middle ear development are described to illustrate how the alteration of molecularly-controlled morphogenetic programs led to phylogenetic modifications of skeletal development. Ontogenetic plasticity has enabled the diversification of jaw elements as well as middle ear structures during evolution. This article is part of a special issue entitled "MEMRO 2012". Copyright © 2013 Elsevier B.V. All rights reserved.

PMID 23396272

Fetal development of the elastic-fiber-mediated enthesis in the human middle ear

Ann Anat. 2013 Oct;195(5):441-8. doi: 10.1016/j.aanat.2013.03.010. Epub 2013 May 1.

Takanashi Y1, Shibata S, Katori Y, Murakami G, Abe S, Rodríguez-Vázquez JF, Kawase T.


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. Copyright © 2013 Elsevier GmbH. All rights reserved. KEYWORDS: Ear ossicles; Elastic fibers; Elastin; Enthesis; Human fetus; Hyaluronan

PMID 23706648


Initial stage of fetal development of the pharyngotympanic tube cartilage with special reference to muscle attachments to the tube

Anat Cell Biol. 2012 Sep;45(3):185-92. doi: 10.5115/acb.2012.45.3.185. Epub 2012 Sep 30.

Katori Y1, Rodríguez-Vázquez JF, Verdugo-López S, Murakami G, Kawase T, Kobayashi T.

Abstract Fetal development of the cartilage of the pharyngotympanic tube (PTT) is characterized by its late start. We examined semiserial histological sections of 20 human fetuses at 14-18 weeks of gestation. As controls, we also observed sections of 5 large fetuses at around 30 weeks. At and around 14 weeks, the tubal cartilage first appeared in the posterior side of the pharyngeal opening of the PTT. The levator veli palatini muscle used a mucosal fold containing the initial cartilage for its downward path to the palate. Moreover, the cartilage is a limited hard attachment for the muscle. Therefore, the PTT and its cartilage seemed to play a critical role in early development of levator veli muscle. In contrast, the cartilage developed so that it extended laterally, along a fascia-like structure that connected with the tensor tympani muscle. This muscle appeared to exert mechanical stress on the initial cartilage. The internal carotid artery was exposed to a loose tissue facing the tubal cartilage. In large fetuses, this loose tissue was occupied by an inferior extension of the temporal bone to cover the artery. This later-developing anterior wall of the carotid canal provided the final bony origin of the levator veli palatini muscle. The tubal cartilage seemed to determine the anterior and inferior margins of the canal. Consequently, the tubal cartilage development seemed to be accelerated by a surrounding muscle, and conversely, the cartilage was likely to determine the other muscular and bony structures. KEYWORDS: Human fetuses; Internal carotid artery; Levator veli palatini muscle; Pharyngotympanic tube cartilage; Tensor tympani muscle PMID 23094207


Closure of the middle ear with special reference to the development of the tegmen tympani of the temporal bone

J Anat. 2011 Apr 8. doi: 10.1111/j.1469-7580.2011.01378.x. [Epub ahead of print]

Rodríguez-Vázquez JF, Murakami G, Verdugo-López S, Abe SI, Fujimiya M. Department of Anatomy and Human Embryology II, Faculty of Medicine, Embryology Institute, University Complutense of Madrid, Spain Division of Internal Medicine, Iwamizawa Kojin-kai Hospital, Iwamizawa, Japan Oral Health Science Center HRC7, Tokyo Dental College, Chiba-City, Chiba, Japan Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.

Abstract Closure of the middle ear is believed to be closely related to the evolutionary development of the mammalian jaw. However, few comprehensive descriptions are available on fetal development. We examined paraffin-embedded specimens of 20 mid-term human fetuses at 8-25 weeks of ovulation age (crown-rump length or CRL, 38-220 mm). After 9 weeks, the tympanic bone and the squamous part of the temporal bone, each of which was cranial or caudal to Meckel's cartilage, grew to close the lateral part of the tympanosquamosal fissure. At the same time, the cartilaginous tegmen tympani appeared independently of the petrous part of the temporal bone and resulted in the petrosquamosal fissure. Subsequently, the medial part of the tympanosquamosal fissure was closed by the descent of a cartilaginous inferior process of the tegmen tympani. When Meckel's cartilage changed into the sphenomandibular ligament and the anterior ligament of the malleus, the inferior process of the tegmen tympani interposed between the tympanic bone and the squamous part of the temporal bone, forming the petrotympanic fissure for the chorda tympani nerve and the discomalleolar ligament. Therefore, we hypothesize that, in accordance with the regression of Meckel's cartilage, the rapidly growing temporomandibular joint provided mechanical stress that accelerated the growth and descent of the inferior process of the tegmen tympani via the discomalleolar ligament. The usual diagram showing bony fissures around the tegmen tympani may overestimate the role of the tympanic bone in the fetal middle-ear closure. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

PMID 21477146

Can you hear me now? Understanding vertebrate middle ear development

Front Biosci. 2011 Jan 1;16:1675-92.

Chapman SC. Clemson University, Biological Sciences, 132 Long Hall, Clemson, SC 29634, USA. schapm2@clemson.edu


The middle ear is a composite organ formed from all three germ layers and the neural crest. It provides the link between the outside world and the inner ear, where sound is transduced and routed to the brain for processing. Extensive classical and modern studies have described the complex morphology and origin of the middle ear. Non-mammalian vertebrates have a single ossicle, the columella. Mammals have three functionally equivalent ossicles, designated the malleus, incus and stapes. In this review, I focus on the role of genes known to function in the middle ear. Genetic studies are beginning to unravel the induction and patterning of the multiple middle ear elements including the tympanum, skeletal elements, the air-filled cavity, and the insertion point into the inner ear oval window. Future studies that elucidate the integrated spatio-temporal signaling mechanisms required to pattern the middle ear organ system are needed. The longer-term translational benefits of understanding normal and abnormal ear development will have a direct impact on human health outcomes.

PMID 21196256


Development of the stapedius muscle canal and its possible clinical consequences

Int J Pediatr Otorhinolaryngol. 2011 Feb;75(2):277-81. Epub 2010 Dec 10.

Cisneros A, Orozco JR, Nogues JA, Gotor CY, Orozco AW, de la Torre MA, Gil AV. Department of Human Anatomy and Histology, School of Medicine, University of Zaragoza, C/ Domingo Miral, s/n, 50009 Zaragoza, Spain. aicisner@unizar.es


OBJECTIVE: To study the development of the stapedius muscle canal in human embryos and foetuses. MATERIALS AND METHODS: 46 temporal bones with ages between 9mm and new-borns were studied. The preparations were dyed using Martins' trichrome technique. RESULTS: Two areas of different embryological origin form the stapedius muscle canal, which contains this muscle and the facial nerve. On the otic capsule, at 11 weeks an extension starts to grow from its caudal part, which moves outwards and near to Reichert's cartilage, forming the footplate and internal wall. The pyramidal eminence comes from the mesenchyme that surrounds the muscle, forming a partition to separate it from the laterohyale portion of Reichert's cartilage. Extensive connections are observed in its development between bone marrow and mesenchyme. At 35 weeks the muscle and nerve start to separate by means of a bony partition. If this partition does not form, there is going to be a dehiscence that could cause peripheral nerve pathology due to the repeated contraction of the muscle, or the dissemination of infections from middle ear. CONCLUSION: During the development of the stapedius muscle canal the presence of dehiscences between the facial nerve and the muscle may have clinical repercussions.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID 21145599


History of studies on mammalian middle ear evolution: a comparative morphological and developmental biology perspective

J Exp Zool B Mol Dev Evol. 2010 Sep 15;314(6):417-33.

Takechi M, Kuratani S. Source Evolutionary Morphology Research Group, Center for Developmental Biology, RIKEN, Kobe,Hyogo, Japan. sabaidee@cdb.riken.jp


The mammalian middle ear represents one of the most fundamental morphological features that define this class of vertebrates. Its skeletal pattern differs conspicuously from those of other amniotes and has attracted the attention of comparative zoologists for about 200 years. To reconcile this morphological inconsistency, early comparative morphologists suggested that the mammalian middle ear was derived from elements of the jaw joint of nonmammalian amniotes. Fossils of mammalian ancestors also implied a transition in skeletal morphology that resulted in the mammalian state. During the latter half of the 20th century, developmental mechanisms controlling the formation of the jaw skeleton became the subject of studies in developmental biology and molecular genetics. Mammalian middle ear evolution can now be interpreted as a series of changes in the developmental program of the pharyngeal arches. In this review, we summarize the history of middle ear research, highlight some of the remaining problems, and suggest possible future directions. We propose that to understand mammalian middle ear evolution, it is essential to identify the critical developmental events underlying the particular mammalian anatomy and to describe the evolutionary sequence of changes in developmental and molecular terms. We also discuss the degree of consistency between the developmental explanation of the mammalian middle ear based on molecular biology and morphological changes in the fossil record.

(c) 2010 Wiley-Liss, Inc.

PMID 20700887

Development of the stapedius muscle and unilateral agenesia of the tendon of the stapedius muscle in a human fetus

Anat Rec (Hoboken). 2010 Jan;293(1):25-31.

Rodríguez-Vázquez JF, Mérida-Velasco JR, Verdugo-López S. Departamento de Anatomía y Embriología Humana II, Facultad de Medicina, Universidad Complutense, Madrid, España. jfrodvaz@med.ucm.es


The objective was to analyze the development of the stapedius muscle to understand an isolated unilateral absence of the tendon of the stapedius muscle in a human fetus. The study was made on 50 human embryos and fetuses aged 38 days to 17 weeks post-conception. The stapedius muscle was formed by two anlagen, one for the tendon, which derives from the internal segment of the interhyale and another for the belly, located in the second pharyngeal arch, medially to the facial nerve and near the interhyale. In the interhyale, two segments were observed forming an angle and delimited by the attachment of the belly of the stapedius muscle. The internal segment will form the tendon. The lateral segment of the interhyale was attached to the cranial end of the Reichert's cartilage (laterohyale), and normally it disappears at the beginning of the fetal period. The right unilateral agenesia of the tendon of the stapedius muscle, observed for the first time in a human fetus of 14 weeks post-conception development (PCd), was brought about by the lack of formation or the regression of the internal segment of the interhyale. It presented a belly of the stapedius muscle with an anomalous arrangement, and with a pseudo tendon originated by the persistence of the external segment of the interhyale. (c) 2009 Wiley-Liss, Inc.

PMID 19899117

Defects in middle ear cavitation cause conductive hearing loss in the Tcof1 mutant mouse

Hum Mol Genet. 2010 Apr 15;19(8):1551-60. Epub 2010 Jan 27.

Richter CA, Amin S, Linden J, Dixon J, Dixon MJ, Tucker AS. Source Department of Craniofacial Development, Dental Institute, King's College London, London SE1 9RT, UK.


Conductive hearing loss (CHL) is one of the most common forms of human deafness. Despite this observation, a surprising gap in our understanding of the mechanisms underlying CHL remains, particularly with respect to the molecular mechanisms underlying middle ear development and disease. 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. This research provides important insights into a poorly characterized cause of human deafness, and provides the first mouse model for the study of middle ear cavity defects, while also being of direct relevance to a human genetic disorder.

PMID 20106873 http://www.ncbi.nlm.nih.gov/pubmed/20106873


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

Amin S, Matalova E, Simpson C, Yoshida H, Tucker AS. BMC Dev Biol. 2007 Dec 5;7:134.

PMID 18053235

"The malleus and incus first appear as a single united condensation expressing early cartilage markers. The incudomalleal joint region forms by cells in the presumptive joint region switching off cartilage markers and turning on joint markers. Failure in this process may result in fusion of this joint, as observed in human syndromes such as Branchio-Oto-Renal Syndrome or Treacher Collins Syndrome."

Anat Anz. 1990;171(3):187-91. [The morphometry of the ear ossicles in humans during development] [Article in German] Olszewski J. Anstalt für Normale Anatomie, Medizinischen Militärakademie Lódź, Polen. Abstract The dimensions and the mass of the auditive ossicles was determined bilaterally in 100 human fetuses, of each sex aged from 21 to 40 weeks and 20 individual adults aged 18 to 40 years. It was found that the development of auditive ossicles in human is not completed during fetal life. The analyzed parameters of malleus (a, b, c, d1, d2, e) in the over fetal life period increased adequately by 14.02%, 11.22%, 16.70%, 12.80%, 12.01%, 21.98%, incus by (a, b, c1, c2, d, e) - 7.61%, 11.48%, 11.40%, 23.59%, 12.14%, 14.94%, stapes by (a, b, c, d, e, f) - 6.28%, 7.66%, 8.40%, 4.54%, 4.54%, 4.16%. In the over fetal life period increase of weight of malleus by 22.05%, incus by 26.49%, stapes by 11.57% was also observed. Described parameters of ossicles system are very important with respect to classification to the operations improving hearing in the system convecting of vibration of the tympanic membrane in children.

PMID 2268059


Development of the stapes and associated structures in human embryos

J Anat. 2005 Aug;207(2):165-73.

Rodríguez-Vázquez JF. Departamento de Anatomía y Embriología Humana II, Facultad de Medicina, Universidad Complutense, Madrid, Spain. jfrodvaz@med.ucm.es


The objective of this study was to clarify the development of the stapes in humans and its relationship with the cartilage of the second branchial arch. The study was carried out in 25 human embryos between 6 and 28 mm crown-rump length. The stapes develops at the cranial end of the second branchial arch through an independent anlage of the cartilage of this arch. Between the stapedial anlage and the cranial end of the Reichert's cartilage there is a formation called the interhyale, the internal segment of which gives rise to the tendon of the stapedial muscle. The stapedial anlage is a unique formation with two distinct parts: the superior part that will comprise the base and the inferior part that will be crossed by the stapedial artery during embryonic development and will constitute the limbs and the head of the stapes. According to the results, the otic capsule is not involved in formation of the base of the stapes.

PMID 16050903


A microanalytical study on human auditory ossicles in normal and pathological conditions

Acta Otolaryngol. 1992;112(2):317-21.

Sánchez-Fernández JM, Saint-Gerons S, Sánchez del Rey A. Source Department of Otolaryngology, School of Medicine, University of the Basque Country, Bilbao, Spain.


A microanalytical study of human auditory ossicles was performed in 11 normal adults, 13 infants, 13 foetuses, 7 middle ear cholesteatoma, 7 chronic otitis and 1 facial nerve schwannoma. Malleus and incus ossification is initiated in the foetal period, the Ca/P ratio reaching a value of 1.8-1.9 in the 29-gestation-week foetus and continues in the infant period until adult, except for the marginal area of the malleus head which appears mineralized in the infant. The normal Ca/P ratio for malleus is 2.10, and 2.19 for incus. In the stapes, mature Ca/P ratio values (2.11) appear in the footplate of the 23-gestation-weeks foetus. Stapes ossification continues in its head and crura, but never reaches malleus and incus values. We have confirmed that there is a relationship between Ca/P ratio and sulphur values in the ossification process; so when the first increases the second decreases. Finally, in our pathological material we have not found any significant alteration of Ca/P ratio, sulphur or other elements studied.

PMID 1604999