Talk:Hearing - Middle Ear Development

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


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.


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.


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.


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.


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


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.


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