Hearing - Inner Ear Development

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Introduction

Adult hearing embryonic origins cartoon
Adult hearing embryonic origins.
Otic placodes electron micrograph
Otic placodes (Stage 11 dorsal view)
Historic images - The membranous labyrinth
Historic images - The membranous labyrinth

The inner ear is derived from a pair of surface sensory placodes (otic placodes) that appear in human development during week 4 (GA week 6) in the head region lying behind the second pharyngeal arch.


These otic placodes fold inwards forming initially a depression, then pinch off entirely from the surface forming an epithelium surrounding a fluid-filled sac or vesicle (otic vesicle, otocyst, auditory vesicle). The vesicle sinks into the head mesenchyme some of which closely surrounds the otocyst forming the otic capsule.

The otocyst finally lies close to the early developing hindbrain (rhombencephalon) and the developing vestibulo-cochlear-facial ganglion complex.


The otocyst epithelium then undergoes a series of morphological changes, forming the primitive membranous labyrinth. During the human fetal period this will differentiate into the inner ear components for hearing (cochlea) and balance (semi-circular canals).

The adult cochlear has a "snail-shell" appearance, with the total number of turns differing between species. The adult human cochlear is typically described as having 2.5 turns, but this can vary up to 2.75 or even 3 turns.[1]

The "organ of corti" that develops within the cochlea was first identified by Alfonso Giacomo Gaspare Corti (1822–1876), an Italian anatomist, in 1851.

Hearing Links: Introduction | Science Lecture | Lecture Movie | 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

Categories: Hearing | Outer Ear | Middle Ear | Inner Ear

Historic Embryology 
Historic Embryology: 1880 Platypus cochlea | 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 | 1932 Otic Capsule 1 | 1933 Otic Capsule 2 | 1936 Otic Capsule 3 | 1933 Endolymphatic Sac | 1934 Otic Vesicle | 1934 Membranous Labyrinth | 1938 Stapes - 7 to 21 weeks | 1938 Stapes - Term to Adult | 1942 Stapes - Embryo 6.7 to 50 mm | 1943 Stapes - Fetus 75 to 150 mm | 1948 Stapes - Fetus 160 mm to term | 1959 Auditory Ossicles | 1963 Human Otocyst | Historic Disclaimer

Some Recent Findings

  • Lineage tracing of Sox2-expressing progenitor cells in the mouse inner ear reveals a broad contribution to non-sensory tissues and insights into the origin of the organ of Corti[2] "The transcription factor Sox2 is both necessary and sufficient for the generation of sensory regions of the inner ear. ...We find that Sox2-expressing cells in the early otocyst give rise to large numbers of non-sensory structures throughout the inner ear, and that Sox2 only becomes a truly prosensory marker at embryonic day (E)11.5. Our fate map reveals the organ of Corti derives from a central domain on the medial side of the otocyst and shows that a significant amount of the organ of Corti derives from a Sox2-negative population in this region." Developmental Signals - Sox | Mouse Development
  • Development of the stria vascularis and potassium regulation in the human fetal cochlea[3] "We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9-W18) and show the cochlear expression dynamics of key potassium-regulating proteins. At W12, MITF+/SOX10+/KIT+ neural-crest-derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na+ /K+ -ATPase-positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament."
  • Distribution and development of peripheral glial cells in the human fetal cochlea[4] "The adult human cochlea contains various types of peripheral glial cells that envelop or myelinate the three different domains of the spiral ganglion neurons: the central processes in the cochlear nerve, the cell bodies in the spiral ganglia, and the peripheral processes in the osseous spiral lamina. ...The developmental dynamics of the peripheral glial cells in the human fetal cochlea is in support of a neural crest origin. Our study provides the first overview of the distribution and maturation of peripheral glial cells in the human fetal cochlea from W9 to W22." Neural Crest Development
  • Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells[5] "Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. ...The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation." Sonic hedgehog
  • Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis.[6]"These results indicate that Tbx1 expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity."
More recent papers
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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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Search term: Inner Ear Development'

Zhichao Song, Azadeh Jadali, Bernd Fritzsch, Kelvin Y Kwan NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors. Stem Cell Reports: 2017; PubMed 29033307

Sanam Zarei, Kasra Zarei, Bernd Fritzsch, Karen L Elliott Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear. Dev Neurobiol: 2017; PubMed 29030893

Keiji Honda, Sung Huhn Kim, Michael C Kelly, Joseph C Burns, Laura Constance, Xiangming Li, Fei Zhou, Michael Hoa, Matthew W Kelley, Philine Wangemann, Robert J Morell, Andrew J Griffith Molecular architecture underlying fluid absorption by the developing inner ear. Elife: 2017, 6; PubMed 28994389

Maryline Beurg, Robert Fettiplace PIEZO2 as the anomalous mechanotransducer channel in auditory hair cells. J. Physiol. (Lond.): 2017; PubMed 28983916

Killian S Hanlon, Naomi Chadderton, Arpad Palfi, Alfonso Blanco Fernandez, Peter Humphries, Paul F Kenna, Sophia Millington-Ward, G Jane Farrar A Novel Retinal Ganglion Cell Promoter for Utility in AAV Vectors. Front Neurosci: 2017, 11;521 PubMed 28983234

Otic Placode

otic placode
Stage 12 otic placode

The embryonic surface sensory placode associated with hearing and balance. This will be lost from the embryo surface to form the otocyst or otic vesicle.

  • Stage 11 - single layer of ectodermal cells organized in a columnar epithelium, which differs in cell shape from the surrounding cuboidal epithelia that will contribute the epithelia of the skin.
    • zebrafish model - a number of specific genes are involved in initial induction of the otic placode including both growth factors (fgf3 and fgf8) and transcription factors (dlx3b, dlx4b, and foxi1).[7]
  • Proliferation of the otic placode cells leads to an inward folding, or invagination, giving the external appearance of a depression on the lateral sides of the early developing neck region.
  • The epithelium is still a single layer of cells, which continues to invaginate until the edges of the disc of cells come into apposition on the embryo surface.
    • mouse model - placodal invagination but not specification requires placodal expression of the transcription factor Sox9.[8]

Sensory Placodes

  • Week 4 a series of thickened surface ectodermal patches form in pairs rostro-caudally in the head region.
    • Recent research suggests that all sensory placodes may arise from common panplacodal primordium origin around the neural plate, and then differentiate to eventually have different developmental fates.
  • Each pair of sensory placodes will later contribute key components of each of our special senses (hearing, vision, smell and taste).
    • Otic Placode - one of the first to form and contributes inner ear structures.
    • Optic (Lens) Placode - lies on the surface, adjacent to the outpocketing of the nervous system (which will for the retina) and will form the lens.
    • Nasal Placode - 2 components (medial and lateral) and will form the nose olefactory epithelium.
  • Other species have a number of additional placodes which form other sensory structures (fish, lateral line receptor).
  • Note that their initial postion on the developing head is significantly different to their final position in the future sensory system.


Links: Placodes | Week 4

Otocyst

The otocyst will differentiate to form all components of the membranous labyrinth. The organ of Corti forms initially from the central domain on the medial side of the otocyst.[2] Sox2 regulates organ of Corti prosensory progenitor development, through Jag1 (Notch ligand) signaling.

Histology of otocyst

Stage 13 otic vesicle now lies beneath the embryo surface.

  • Stage 13 - the otic placode has sunk from the surface ectoderm to form a hollow epithelial ball, the otocyst (otic vesicle), which now lies beneath the surface surrounded by mesenchyme (mesoderm and neural crest).
  • The epithelia of this ball varies in thickness and has begun to distort, it will eventually form the inner ear membranous labyrinth.
  • forms otocyst
  • branches form and generate endolymphatic duct and sac
  • forms vestibular (dorsal) and cochlear (ventral) regions
  • differentiation of otic vesicle to membranous labyrinth

Week 5

Stage 13 embryo (week 5) showing otocyst that will form the inner ear.

Stage13 otocyst

A. Ventrolateral view of the whole embryo with 5-mm scale bar. At this stage of development no middle or external ear structures are apparent and will be derived later from pharyngeal arches one and two (labeled). B. The gray bar through the head indicates the plane of cross-section, which is a cross-section of the head showing the size and position of the otic vesicles. At this stage of development they lie within the head mesenchyme behind pharyngeal arch one and two and in close apposition to the developing hindbrain. Note the close position of the otic vesicle to the rhombomeres, hindbrain folds that represent the initial segmentation of the hindbrain. Also shown are developing cranial ganglia and blood vessel lying adjacent to the otic vesicles. The wall of the otic vesicle at this stage is a simple epithelium.

Week 7

Stage 19 ear.jpg


Week 8

Stage 22 embryo (week 8) showing the embryo near the end of the embryonic period.

Stage22 ear.jpg

A. Lateral view of the whole embryo with 5 mm scale bar. Note the well developed external ear with simplified adult structure and narrower meatal opening. The grey bar through the head indicates the plane of cross-section for (B) and (C). B. Cross-section of the head at the plane of the skull base and oral cavity to the top. The otic capsule is well formed by this stage containing all the membranous labyrinth structures. It is still a cartilaginous structure ventral to the brainstem and lying behind the oral cavity. The tongue occupies the floor of the oral cavity with the unfused palatal shelves lying lateral and the auditory tubes clearly shown on the posterior wall. The external ear is visible on the right hand side of the head with a band of cartilage (dark stain) within the auricle.

C. The gray box indicates this region: detail of inner and middle ear development. The middle ear cavity has not yet formed and the ossicles (malleus shown) are embedded in mesenchyme that is being lost. The tensor tympani muscle is differentiating in the adjacent mesenchyme. The inner ear membranous labyrinth has formed its adult external structure. The section through the turns of the cochlear duct shows the internal cochlea structure is still underdeveloped; in contrast, the balance region is more developed.

The Membranous Labyrinth

Gray0924.jpg


Fetal

Week 8.4

Human fetal cochlea basal turn week 8.4

Human fetal cochlea basal turn week 8.4 Gestational Week GA 10.4 (Stain - Haematoxylin Eosin)[9]

Week 10

Human fetal cochlea basal turn week 10

Human fetal cochlea basal turn week 10 Gestational Week GA 12 (Stain - Haematoxylin Eosin)[9]

Week 18 - 22

Developmental data from an EM study of the human organ of corti.[10] Original GA data has been recalculated as fertilisation ages.

Week Event
18 stria vascularis, tectorial membrane, afferent nerve ending
20 Nuel space, stereocilia maturation, efferent nerve ending
22 tunnel of corti, kinocilium, space between hair and supporting cell
Week 18 Week 20 Week 22
  • stria vascularis - 18-20 weeks (GA 20 week 3 days - 22 week)
  • tectorial membrane - 18 weeks (GA 20 week 3 days)
  • Afferent nerve ending - 18 weeks (GA 20 week 3 days)
  • Nuel space - 20 weeks (GA 22 week 0 days - 24 week)
  • Efferent nerve ending - 20 weeks (GA 22 week 0 days)
  • Maturation of stereocilia - 20 weeks (GA 22 week 0 days - 24 week 0 days)
  • tunnel of corti - GA 24 week
  • Space between hair and supporting cell - 24 week
  • Presence of kinocilium - GA 24 week 0 days

Historic

A series of historic wax-plate reconstructions of the membranous labyrinth and the surrounding periotic tissue-spaces showing development stages (median and lateral views) of these spaces at the same scale (ages are only approximations calculated on CRL).

Human Fetal Membranous Labyrinth Development
Fetus 50 mm CRL 10 weeks (GA 12)
Human fetus 10 weeks 50 mm CRL Streeter027.jpg
lateral view median view
Fetus 85 mm CRL 14 weeks (GA 16)
Streeter028.jpg Streeter029.jpg
lateral view median view
Fetus 130 mm CRL 15 weeks (GA 17)
Streeter030.jpg Streeter031.jpg
lateral view median view


Links: Growth of the Otic Capsule (1918) | Fetal CRL | Fetal Development

Fetal Cochlea Molecular

Human fetal cochlea basal turn by Gestational Week GA[9]

Human cochlea fetal development cartoon

Abbreviations

  • SGN - spiral ganglion neuron
  • IHC - inner hair cell
  • O1 - first row of outer hair cells
  • O2 - second row of outer hair cells
  • O3 - third row of outer hair cells
  • OHC - outer hair cell.
Gestational Week GA

Week 10 (W10) - SOX2 identifies the prosensory domain within the SOX9/SOX10+ cochlear duct epithelium. Neurites from the adjoining TUBB3+/PRPH + SGNs do not yet penetrate into the epithelium.






Week 11 (W11) - Penetration starts prior to hair cell differentiation.






Week 12 (W12) - The first MYO7A+/SOX9-/SOX10-/SOX2+ (inner) hair cell can be seen, and is contacted by multiple TUBB3+ and PRPH + neurites. Penetrating neurites are also found at the location of the future OHCs.






Week 14 (W14) - Both the IHCs and OHCs have differentiated, and neurites underneath the OHCs start to run in a spiral direction. At this stage, hair cells still express SOX2.






Week 20 (W20) - SOX2 is downregulated in all hair cells, as opposed to the other cells in the organ of Corti. PRPH expression distinguishes between type I (PRPH-) and type II (PRPH+) neurites.


Organ of Corti

Within the cochlea, the specialised structure required for converting mechanical vibration into an electrical signal occurs at the organ of corti.

The images (mouse) below show the detail of the specialised structure, the organ of Corti, that develops through the fetal period.

Mouse organ of corti 01.jpg Mouse organ of corti 02.jpg
Mouse organ of corti 03.jpg Mouse organ of corti 05.jpg


Endolymphatic Sac

  • the adult endolymphatic sac is filled with endolymphatic fluid
  • with a unique composition of high potassium and low sodium ions
  • it is not known in humans at what stage of development this ionic status is achieved
    • In the rat, adult sodium levels are seen in the first week after birth, while both potassium and chloride levels were below the normal adult levels.
Mouse organ of corti 04.jpg

Vestibular Sac

  • generates 3 expansions - form semicircular ducts
  • remainder forms utricle
  • epithelia lining generates - hair cells, ampullary cristae, utricular macula
  • Vestibular - Otoconia, otoconin- inner ear biominerals

Cochlear Sac

Cochlear Sac[3]
  • generates coiled cochlear duct (humans 2 1/2 turns)
  • remainder forms saccule
  • epithelia lining generates
  • hair cells
  • structures of organ of corti
  • saccular macula

Scala Media

three spiral passages of cochlea

(Latin, medius = middle) spiral of middle cochlear duct lying between scala vestibuli and scala tympani, containing endolymph.

Scala Tympani

(Latin, tympanon = drum) the spiralling cochlear duct below spiral lamina, containing perilymph and ending at round window near tympanic membrane.

Scala Vestibuli

(Latin, vestibulum = cavity at beginning of canal) the spiralling cochlear duct above spiral lamina, containing perilymph, beginning near the vestbule and ending where it communicates with the scala tympani at the helicotrema.


Endolymph

  • extracellular fluid secreted by the stria vascularis.
  • potassium is the main cation required for depolarizing electrical current in the hair cells.

Perilymph

  • extracellular fluid similar in composition to either plasma or cerebrospinal fluid.
  • sodium is the main cation.
Inner ear hair cells


Stria Vascularis

stria vascular histology Cochlea stria vascularis cartoon 03.jpg
In the adult the stria vascularis functions to synthesise and secretes endolymph. The three main cell types within the stria that have different embryological origins and are connected by different forms of cell junctions. Anatomical (upper half) and compartmental (lower half) model of the adult stria vascularis showing the three cellular layers and depicting the location of potassium regulating channels. The stria vascularis is electrochemically isolated from neighboring structures by tight junctions (black bars).[3]
Marginal cells Intermediate cells Basal cells
line the lumen of the cochlear duct melanocyte-like cells lie between the marginal and basal cell layers mesenchymal spiral ligament fibrocytes
derived from epithelia. derived from the neural crest. derived from otic mesenchyme.[11]

Mouse SEM

The gallery below shows scanning electron micrographs of the developing mouse (E18.5) cochlea.[12]

Adult Cochlea

Max Brödel-cochlea drawing1934.jpg

Adult inner ear (Max Brödel 1934)

Magnetic Resonance Images of the Adult Cochlea[13]
Cochlea MRI 01.jpg Cochlea MRI 02.jpg

The investigators used a method to obtain magnetic resonance imaging (MRI) to measure cochlear length from the temporal bones of 6 cadavers. By overlapping digitalized rulers on these images it was possible to measure cochlear length. Adult cochlear length varied between 17 and 26.5 millimeters.[13]

Mouse E18.5 cochlea sem05.jpg

Mouse cochlea (SEM) showing organization of the hair cells.[14]


Mouse Cochlea Links: Cochlea overview SEM | Base region SEM | Mid-base and Apex region SEM | Mid-base region SEM | Mid-base hair cells SEM | Mouse Development

Bony Labyrinth

  • formed from chrondified mesoderm
  • Periotic Capsule
  • mesenchyme within capsule degenerates to form space filled with perilymph

Auditory Neural Pathway

Hearing sound localization circuits brainstem

Central auditory neural pathway

Keith1902 fig046.jpg

Vestibulocochlear Nerve

Adult cochlea cartoon 01.jpg
Adult cochlea nerve glia cartoon[4]
Afferent (sensory) cranial nerve brainstem primary terminal nuclei
  • forms beside otocyst
  • from wall of otocyst and neural crest cells
  • bipolar neurons

Vestibular Neurons

  • outer end of internal acoustic meatus
  • innervate hair cells in membranous labyrinth
  • axons project to brain stem and synapse in vestibular nucleus

Cochlear Neurons

  • cell bodies lie in modiolus
  • central pillar of cochlear
  • innervate hair cells of spiral organ
  • axons project to cochlear nucleus
Links: Hearing - Neural Pathway

Cochlea Glial

Cochlea glial lineage cartoon.jpg Adult cochlea nerve glia cartoon.jpg
Cochlea glial lineage [4] Adult cochlea nerve glia cartoon[4]


Links: Hearing - Neural Pathway

Inner Ear Genes

  • hindbrain segmentation occurs at same time placode arises
  • otocyst adjacent to rhombomere 5
    • may influence development
  • Hoxa1, kreisler, Fgf3
  • genes regulating neural crest cells (neural genes)
  • Pax2 Ko affects cochlear and spiral ganglion, but not vestibular apparatus
  • nerogenin 1 affects both ganglia
  • LIN28B - RNA-binding protein times auditory prosensory cell cycle withdrawal and differentiation through both let-7–dependent and independent mechanisms.[15]

Semicircular canal

  • Otx1- cochlear and vestibular normal
  • Hmx3, Prx1, Prx2

Sensory Organs

  • thyroid hormone receptor beta
  • Zebrafish-mindbomb mutant has excess hair cells but not supporting cells, Notch-Delta signaling
  • Gene Expression-inner ear
  • Brn-3c and Hair cell development
  • Supporting Cells- p27kip
  • Thyroid Hormone
  • Ganglion neurons require growth factors
  • vestibular neurons- BDNF, NT3
    • survival not development

Sox9 20346939 Sox2 20071536

Other Species Overview

Inner ear development cartoon 01.jpg

Comparison of zebrafish and late stage chick and mouse embryos[16]

Zebrafish Development Chicken Development | Mouse Development

(a) Formation of the pre-placodal region (PPR), otic placode and otocyst (otic vesicle) from cranial ectoderm. The otocyst is the source of nearly all cell types of the mature ear.

(b) Otic neurogenesis: neuroblasts are specified from otic vesicle epithelium, but delaminate from it and accumulate beneath the ear in a transit amplifying population (light blue). Neurons (dark blue) differentiate from this population, and innervate sensory hair cells in the overlying otic epithelium. The ganglion develops in close association with neural crest cells (green), which give rise to glia.

(c) Early otolith formation in the zebrafish otic vesicle. At least three distinct populations of cilia can be distinguished: immotile hair cell kinocilia (red), which tether the otolith at early stages; motile cilia (blue) in the vicinity of the sensory hair cells, which do not bind otolithic material, and shorter immotile cilia (green).

(d) Schematic comparison of semicircular canal formation in the zebrafish ear (top row) and a generalised amniote ear (bottom row). A single canal is illustrated for clarity. Epithelia adhere at a fusion plate, from which cells are cleared to make the duct. The end result of both events is the same (right hand image), but the fusion plate is much smaller in the zebrafish.

(e) Comparative sketches of inner ears from adult zebrafish and late stage chick and mouse embryos. Sensory (red), neuronal (blue) and endolymph-regulating (yellow) cells are shown for the mouse ear.


Abbreviations: A, ampulla; BP, basilar papilla; HC, hair cell; L, lagena; LM, lagenar macula; MN, maturing neurons; NB, neuroblasts; NCC, neural crest cells; NP, neural plate; Nt, notochord; ooC, organ of Corti; Ot, otolith; OV, otic vesicle; PPR, preplacodal region; S, saccule; SVG, spiral and vestibular ganglion; TA, transit amplifying population of neuroblasts; U, utricle.

(text from original figure legend)

Mouse

  • Dual embryonic origin of the mammalian otic vesicle forming the inner ear[17] "The inner ear and cochleovestibular ganglion (CVG) derive from a specialized region of head ectoderm termed the otic placode. During embryogenesis, the otic placode invaginates into the head to form the otic vesicle (OV), the primordium of the inner ear and CVG. Non-autonomous cell signaling from the hindbrain to the OV is required for inner ear morphogenesis and neurogenesis. In this study, we show that neuroepithelial cells (NECs), including neural crest cells (NCCs), can contribute directly to the OV from the neural tube. ...This study defines a dual cellular origin of the inner ear from sensory placode ectoderm and NECs, and changes the current paradigm of inner ear neurosensory development."


References

  1. Slavomir Biedron, Martin Westhofen, Justus Ilgner On the number of turns in human cochleae. Otol. Neurotol.: 2009, 30(3);414-7 PubMed 19225438
  2. 2.0 2.1 Rende Gu, Rogers M Brown, Chih-Wei Hsu, Tiantian Cai, Alyssa Crowder, Victor G Piazza, Tegy J Vadakkan, Mary E Dickinson, Andrew K Groves Lineage tracing of Sox2(-)expressing progenitor cells in the mouse inner ear reveals a broad contribution to non-sensory tissues and insights into the origin of the organ of Corti. Dev. Biol.: 2016; PubMed 27090805
  3. 3.0 3.1 3.2 Heiko Locher, John C M J de Groot, Liesbeth van Iperen, Margriet A Huisman, Johan H M Frijns, Susana M Chuva de Sousa Lopes Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss. Dev Neurobiol: 2015; PubMed 25663387 | Dev Neurobiol.
  4. 4.0 4.1 4.2 4.3 Heiko Locher, John C M J de Groot, Liesbeth van Iperen, Margriet A Huisman, Johan H M Frijns, Susana M Chuva de Sousa Lopes Distribution and development of peripheral glial cells in the human fetal cochlea. PLoS ONE: 2014, 9(1);e88066 PubMed 24498246 | PLoS One.
  5. Jinwoong Bok, Colleen Zenczak, Chan Ho Hwang, Doris K Wu Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells. Proc. Natl. Acad. Sci. U.S.A.: 2013, 110(34);13869-74 PubMed 23918393
  6. Evan M Braunstein, Dennis C Monks, Vimla S Aggarwal, Jelena S Arnold, Bernice E Morrow Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis. BMC Dev. Biol.: 2009, 9;31 PubMed 19476657
  7. Keely S Solomon, Su-Jin Kwak, Andreas Fritz Genetic interactions underlying otic placode induction and formation. Dev. Dyn.: 2004, 230(3);419-33 PubMed 15188428
  8. Francisco Barrionuevo, Angela Naumann, Stefan Bagheri-Fam, Volker Speth, Makoto M Taketo, Gerd Scherer, Annette Neubüser Sox9 is required for invagination of the otic placode in mice. Dev. Biol.: 2008, 317(1);213-24 PubMed 18377888
  9. 9.0 9.1 9.2 Heiko Locher, Johan H M Frijns, Liesbeth van Iperen, John C M J de Groot, Margriet A Huisman, Susana M Chuva de Sousa Lopes Neurosensory development and cell fate determination in the human cochlea. Neural Dev: 2013, 8;20 PubMed 24131517 | Neural Dev.
  10. Y Igarashi, T Ishii Embryonic development of the human organ of Corti: electron microscopic study. Int. J. Pediatr. Otorhinolaryngol.: 1980, 2(1);51-62 PubMed 7188054
  11. Mark-Oliver Trowe, Hannes Maier, Marianne Petry, Michaela Schweizer, Karin Schuster-Gossler, Andreas Kispert Impaired stria vascularis integrity upon loss of E-cadherin in basal cells. Dev. Biol.: 2011, 359(1);95-107 PubMed 21925491
  12. Amy E Kiernan, Jingxia Xu, Thomas Gridley The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. PLoS Genet.: 2006, 2(1);e4 PubMed 16410827 | PMC1326221 | PLoS Genet.
  13. 13.0 13.1 Fernando Pochini Sobrinho, Paulo Roberto Lazarini, Hea Jung Yoo, Luiz de Abreu Júnior, Altino de Sá Meira A method for measuring the length of the cochlea through magnetic resonance imaging. Braz J Otorhinolaryngol: 2005, 75(2);261-7 PubMed 19575114 | Braz J Otorhinolaryngol.
  14. Amy E Kiernan, Jingxia Xu, Thomas Gridley The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. PLoS Genet.: 2006, 2(1);e4 PubMed 16410827 | PMC1326221 | PLoS Genet.
  15. Erin J Golden, Ana Benito-Gonzalez, Angelika Doetzlhofer The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea. Proc. Natl. Acad. Sci. U.S.A.: 2015; PubMed 26139524
  16. Tanya T Whitfield Development of the inner ear. Curr. Opin. Genet. Dev.: 2015, 32;112-118 PubMed 25796080 | Curr Opin Genet Dev.
  17. Laina Freyer, Vimla Aggarwal, Bernice E Morrow Dual embryonic origin of the mammalian otic vesicle forming the inner ear. Development: 2011, 138(24);5403-14 PubMed 22110056


Reviews

Yuji Nakajima Signaling regulating inner ear development: cell fate determination, patterning, morphogenesis, and defects. Congenit Anom (Kyoto): 2014; PubMed 25040109

Sumantra Chatterjee, Petra Kraus, Thomas Lufkin A symphony of inner ear developmental control genes. BMC Genet.: 2010, 11;68 PubMed 20637105

Elizabeth C Driver, Matthew W Kelley Specification of cell fate in the mammalian cochlea. Birth Defects Res. C Embryo Today: 2009, 87(3);212-21 PubMed 19750520


Articles

Ksenia Gnedeva, A J Hudspeth SoxC transcription factors are essential for the development of the inner ear. Proc. Natl. Acad. Sci. U.S.A.: 2015; PubMed 26504244

Peter A Santi, Ian Rapson, Arne Voie Development of the mouse cochlea database (MCD). Hear. Res.: 2008, 243(1-2);11-7 PubMed 18603386

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Historic

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Historic Images

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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)

Streeter GL. Developmental Horizons In Human Embryos Description Or Age Groups XIX, XX, XXI, XXII, And XXIII, Being The Fifth Issue Of A Survey Of The Carnegie Collection. (1957) Carnegie Instn. Wash. Publ. 611, Contrib. Embryol., 36: 167-196.

Terms

Hearing Terms  
Hearing and Balance Development
  • altricial animal - Term used to describe an animal born in a helpless state, with incomplete development of sensory systems at birth. For example rats and mice are born with incomplete development of visual and auditory systems. (More? Animal Development)
  • ampulla - Term used to describe an anatomical dilation of a tube or canal lumen. Anatomical description of the opening end of the uterine tube lying above the ovary and the enlarged initial segmeny of the semicircular canals of the inner ear vestibular system. (More? Inner Ear)
  • aneurism - (Greek, aneurysma = a widening, aneurysm) A term used to describe an abnormal widening of a vessel or anatomical tubal structure.
  • aquaeductus vestibuli - see vestibular aqueduct (More? Inner Ear)
  • auditory neuropathy - (AN) abnormality of transmission of sound information to the brain.
  • auditory tube - (eustachian tube) between the middle ear and oral cavity, has a bony (tympanic 1/3) and cartilaginous (pharyngeal 2/3) portion. The main role is equalization of pressure and fluid drainage in the middle ear. (More? Middle Ear)
  • auricular hillock - see hillock (More? Middle Ear)
  • atresia - narrowing, usually of an anatomical tube or cavity.
  • autophagocytosis - (Greek, auto = self, phagy = eating, also called autophagy) a cell death mechanism that uses the cell's own lysosomes to self digest.
  • border cells - columnar cells within the organ of Corti on the medial portion of the basilar membrane. (More? Inner Ear)
  • canalis reuniens - (ductus reuniens, canaliculus reuniens, canalis reuniens, Hensen's canal, Hensen's duct, uniting canal, canalis reuniens of Hensen) short narrow canal connecting the cochlea duct to the saccule. (Victor Hensen, 1835-1924) (More? Inner Ear)
  • cerumen - (ear wax) produced by glands in the skin of the outer portion of the ear canal. (More? Outer Ear)
  • chondrified - the developmental differentiation of cartilage from mesenchye, an embryonic connective tissue.
  • cristae ampullaris - located in the ampulla of the membranous semicircular canals a region with both supporting and hair cells. The hair cell cilia are embedded in the gelatinous cupula. (More? Inner Ear)
  • claudius cells - (cells of Claudius) columnar cells with microvilli overlying the basilar membrane and extend from Hensen's cells to the spiral prominence. Barrier cells that lie external to the organ of corti in endolymph. (More? Inner Ear)
  • cochlear sac - embryonic structure, which will form the coiled cochlear duct and contribute to the saccule. (More? Inner Ear)
  • cochlear aqueduct - a bony channel containing the fibrous periotic duct. It connects the basal turn of the cochlea perilymphatic space with the subarachnoid space of the posterior cranial cavity. (More? Inner Ear)
  • cochlin - major constituent of the inner ear extracellular matrix. (More? Inner Ear)
  • collagen type II - major constituent of the inner ear extracellular matrix. (More? Inner Ear)
  • conductive loss - term used to describe one of the two major classes of hearing loss involving external and middle ear abnormalities (other form is Sensorineural loss).
  • connexins - channel proteins of the gap junctions that allow rapid communication between adjacent cells. The two connexins Cx26 and Cx30 are the major proteins of cochlear gap junctions.
  • connexin 26 - A strikingly high proportion (50%) of congenital bilateral nonsyndromic sensorineural deafness cases have been linked to mutations in the GJB2 coding for the connexin26
  • cupular deposits - basophilic material on the cupulae of the semicircular ducts, an postnatal ageing phenomenon seen in some vestibular labyrinth. (More? Inner Ear)
  • clinical weeks - taken from last menstrual period (LMP) and therefore approximately two weeks before fertilization occurs.
  • Deiters' cells - (outer phalangeal cells)
  • discoidin domain receptor 1 - (DDR1) a tyrosine kinase receptor activated by native collagen, expressed in the basement membrane and with fibrillar collagens. Found in basal cells of the stria vascularis, type III fibrocytes, and cells lining the basilar membrane of the organ of Corti. {Meyer zum Gottesberge, 2008 #1877}
  • ductus utriculosaccularis - (More? Inner Ear)
  • endochondral ossification - the process of bone formation from a pre-existing cartilage template. (More? Middle Ear)
  • endoderm - One of the initial 3 germ cell layers (ectoderm, mesoderm and endoderm) formed by the process of gastrulation. The endoderm forms as a cuboidal epithelium and contributes not only to the trilaminar embryo, but also lines the yolk sac. It will form the entire epithelial lining of the gastrointestinal tract (GIT), contribute to the accessory organs of GIT and also forms the epithelial lining of the respiratory tract.
  • endolymphatic fluid - (endolymph, Scarpa's fluid) fluid that fills all the membranous labyrinth of the inner ear, except for the cochlea scala tympani and scala vestibuli which are filled with perilymph.
  • endolymphatic sac - inner ear structure that has anatomically both an intraosseous and extraosseous component. Th e sac has functions regulating endolymph that are both secretory and absorptive. Also the site of endolymphatic sac tumors either sporadical occurring or associated with the autosomal-dominant von Hippel-Lindau (VHL) disease, due to a germ line mutation. (More? Inner Ear)
  • embryological weeks - taken from the time of fertilization which typically occurs around the middle (day 14), or just after, of the typical 28 day menstrual cycle. (More? Embryonic Development)
  • Emx2 - homeobox gene affecting middle ear and inner ear development.
  • eustachian tube - (auditory tube) A cavity linking the pharynx to the middle ear, which develops from the first pharyngeal pouch. Named after Bartolomeo Eustachi (1500 - 1574) an Italian anatomist. (More? Middle Ear)
  • external auditory meatus - (ear canal) develops from the first pharyngeal cleft. (More? Outer Ear)
  • ear wax - see cerumen. (More? Outer Ear)
  • espins - calcium-resistant actin-bundling proteins enriched in hair cell stereocilia and sensory cell microvilli and spiral ganglion neurons (SGNs)
  • eustachian tube - (auditory tube) between the middle ear and oral cavity, equalization of pressure in the middle ear. (More? Middle Ear)
  • external auditory meatus - (EAM, ear canal) cavity connecting the external ear to the tympanic membrane. The adult human ear canal is about 2.5 cm long and 0.7 cm in diameter. (More? Outer Ear)
  • fenestra ovalis - (oval window) separates the tympanic cavity from the vestibule of the osseous labyrinth. (More? Inner Ear)
  • fenestra rotunda - (round window) separates the tympanic cavity from the scala tympani of the cochlea. (More? Inner Ear)
  • fetus - (foetus) term used to describe human development after the 8th week (10th clinical week, LPM) and covers the developmental periods of second and third trimester.
  • fibroblast growth factor 1 - (Fgf-1) a growth factor released from cochlea sensory epithelium which stimulates spiral ganglion neurite branching.
  • fibroblast growth factor 8 - (Fgf-8) a growth factor released by inner hair cells which regulates pillar cell number, position and rate of development.
  • fibroblast growth factor receptor 3 - (Fgfr-3) a tyrosine kinase receptor with a role in the commitment, differentiation and position of pillar cells in the organ of corti
  • fundamental frequency - (natural frequency) the lowest frequency in a harmonic series, for the female voice this is about 225 Hz.
  • helicotrema - term used to describe the cochlear apex. (More? Inner Ear)
  • Hes - (hairy and enhancer of split) family of factors, which has been shown to be a general negative regulator of neurogenesis (Zheng, 2000).
  • hillock - a small hill, used to describe the six surface elevations on pharyngeal arch one and two. (More? Outer Ear)
  • Incus - (anvil) auditory ossicle (More? Middle Ear)
  • inner phalangeal cells - in the cochlea a single row of cells, that along with and three rows of outer phalangeal cells (Deiter's cells), are the hair cell supporting cells. (More? Inner Ear)
  • inner pillar cells - organ of Corti cells arranged in rows and form a boundary between the single row of inner hair cells and three rows of outer hair cells. These cells have surface-associated microtubule bundles. (More? Inner Ear)
  • inner sulcus - area of the cochlear duct. (More? Inner Ear)
  • internal auditory meatus - (internal acoustic meatus, IAM) Anatomical canal in which CN VII and CN VIII ganglia reside and pass through to the brainstem. This bony canal lies between the posterior surface of the petrous pyramid and the bony labyrinth within the dense petrous bone. Also associated clinically with the site where acoustic neuromas may occur. (More? Inner Ear)
  • kinocilium - inner ear hair cell specialised type of cilium on the cell apex.
  • Kolliker's organ - (Kollicker's organ, greater epithelial ridge) Developing cochlear structure consisting of columnar-shaped supporting cells filling the inner sulcus and lying directly under the tectorial membrane. This transient organ regresses and generates the space of the inner sulcus. Rudolph Albert von Kolliker (1817-1905)?? (More? Inner Ear)
  • lateral semicircular duct
  • limbus -
  • LMP - acronym for last menstrual period, used to clinically measure gestation.
  • malleus - (hammer) auditory ossicle (More? Middle Ear)
  • mastoid process - of temporal bone (More? Middle Ear)
  • Math1 - homolog of the Drosophila proneural gene atonal, necessary and sufficient for the production of hair cells in the mouse inner ear. Negatively regulated by Hes1 and Hes5
  • meatal plug - temporary blockage of the external auditory meatus which forms at the end of the embryonic period and remains present until the seventh month.
  • meatus - anatomical opening, cavity or space (external acoustic meatus, internal auditory meatus)
  • mechano-electrical transduction - (MET) occurs within the cochlear hair cells hair bundle. A mechanical stimulus of the hair bundle causes the tip-links to be tensioned, opening ion channels, resulting in the generation of the cell receptor potential. (More? Inner Ear)
  • Meckel's cartilage - first pharyngeal ach cartilage, located within the mandibular prominence. This cartilage first appears at stage 16, stage 20 the beginning of membranous ossification. Named after Johann Friedrich Meckel, (1781 - 1833) a German anatomist. (http://www.whonamedit.com/doctor.cfm/1840.html) (More? Middle Ear)
  • membranous labyrinth - (More? Inner Ear)
  • mucopolysaccharidosis - (MPS IIIB, Sanfilippo Syndrome type B) abnormality caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop abnormal hearing, and mental functioning culminating in early death.
  • netrin-1 - secreted growth factor, expressed in the organ of Corti and spiral ganglion cells, role in process outgrowth. (More? Inner Ear)
  • otoacoustic emissions testing - (OET) hearing test measures sounds generated by the outer hair cells of the cochlea in response to clicks or tone bursts emitted and recorded by a tiny microphone placed in the infant’s external ear canal. (More? Hearing test)
  • olivocochlear - brainstem cholinergic and GABAergic efferent system that innervates sensory cells and sensory neurons of the inner ear.
  • organ of Corti - (More? Inner Ear)
  • organ of Corti protein II - (OCP-II) cytosolic protein or transcription factor? (More? Inner Ear)
  • otolithic membrane - extracellular matrix that cover the sensory epithelia of the inner ear. (More? Inner Ear)
  • ossicle - (small bone) the individual bone of the three middle ear bones (auditory ossicles), which reduce vibrational amplitude but increase force to drive fluid-filled inner ear. (More? Middle Ear)
  • ossify - (More? Middle Ear)
  • otic capsule -
  • otic cup -
  • otic placode - Embryonic ectodermal epithelium giving rise to inner ear structures. (More? Inner Ear | Placodes)
  • otic vesicle - (More? Inner Ear)
  • otoconin - inner ear biominerals required for vestibular apparatus function. (More? Inner Ear)
  • otogelin - (Otog) an inner ear specific glycoprotein expressed in cochlea cells at different developmental times. (More? Inner Ear)
  • otolithic membrane - a membrane within the utricle and saccule containing embedded hair cell cilia and small crystalline bodies of calcium carbonate (otoliths). Functions to detect head motion.
  • otoliths - small crystalline bodies of calcium carbonate found within the otolitic membrane of the utricle and saccule. (More? Inner Ear)
  • ototoxic - compound or drug causing temporary or permanent hearing loss.
  • outer hair cells - (OHCs) three rows of hair cells that function to increase basilar membrane motion through a local mechanical feedback process within the cochlea, the " cochlear amplifier".
  • outer pillar cells - arranged in rows and form a boundary between the single row of inner hair cells and three rows of outer hair cells. (More? Inner Ear)
  • paratubal musculature - muscles lying beside the auditory (Eustachian) tube. The tensor veli, palatini (TVP) and tensor tympani muscles. (More? Middle Ear)
  • perilymph - perilymphatic space - Periotic Capsule - petrous portion - of temporal bone
  • pejvakin gene - in humans, two missense mutations in this gene cause nonsyndromic recessive deafness (DFNB59) by affecting the function of auditory neurons.
  • pharyngeal arch - (More? Outer Ear) pharyngeal pouch pharyngeal membrane Pharynx
  • pillar cells - (PC) form an inner and outer row of support cells that form a boundary between inner and outer hair cells. (More? Inner Ear)
  • preyer reflex - ear flick in mouse in response to sound.
  • presbyacusis
  • prestin - a motor protein structurally similar to the anion transporter family expressed in cochlear outer hair cells. (More? Inner Ear)
  • preauricular tag - skin tags located in front of the external ear opening, are common in neonates and in most cases are normal, though in some cases are indicative of other associated abnormalities.
  • protocadherin 15 - (Pcdh15) required for initial formation of stereocilia bundles and changes in the actin meshwork within hair cells. The Ames waltzer (av) mouse mutant has both auditory and vestibular abnormalities from a mutation in this gene.
  • Reichert's cartilage - pharyngeal ach 2 cartilage, named after Karl Bogislaus Reichert (1811 - 1883) a German anatomist.
  • Reissner's membrane - (vestibular membrane, vestibular wall) is a membrane located inside the cochlea separating the scala media from scala vestibuli. Named after Ernst Reissner (1824-1878) a German anatomist. It primarily functions as a diffusion barrier, allowing nutrients to travel from the perilymph to the endolymph of the membranous labyrinth.
  • rhombomere -
  • saccular macula -
  • Saccule - (Latin, sacculus = a small pouch)
  • sacculocollic reflex -
  • scala tympani - one of the three Cochlea cavities, it is filled with perilymph.
  • Scarpa's ganglion - (vestibular ganglion) primary afferent vestibular neuron ganglion of the vestibular nerve. Located within the internal auditory meatus. (More? Inner Ear)
  • semicircular canals - series of fluid-filled loops of the inner ear required for balance and sensing acceleration. (More? Inner Ear)
  • sensorineural - term used to describe one of the two major classes of hearing loss involving the central pathway from the cochlear (other form is conductive loss).
  • space of Nuel - within the cochlea, an organ of Corti space between the outer pillar cells and the phalangeal and hair cells. Named after Jean-Pierre Nuel (1847-1920) a Belgian ophthalmologist. (More? Inner Ear)
  • spiral ganglion neurons - (SGN) innervate the inner (Type I) and outer (Type II) hair cells of the cochlea. (More? Inner Ear)
  • stapedius muscle - (innervated by CN VII tympanic branch) one of the two muscles in the middle ear, contraction of this muscle pulls the stapes and dampens auditory ossicle movement. (More? Middle Ear)
  • stapes - (stirrup) a middle ear auditory ossicle (bone) (More? Middle Ear)
  • stapes footplate - (More? Middle Ear)
  • startle response -
  • stereocilia -finger-like projections from the apical surface of sensory hair cells forming the hair bundle in the cochlea. Formed by tightly cross-linked parallel actin filaments in a paracrystalline array with cell surface specializations (tip links, horizontal top connectors, and tectorial membrane attachment crowns).
  • stratified squamous epithelia - classification of epithelium which transiently forms a plug in external ear canal to the outer eardrum.
  • stria vascularis - forms the outer wall of the cochlear duct of the mammalian cochlea is composed primarily of three types of cells. Marginal cells line the lumen of the cochlear duct and are of epithelial origin. Basal cells also form a continuous layer and they may be mesodermal or derived from the neural crest. Intermediate cells are melanocyte-like cells, presumably derived from the neural crest, and are scattered between the marginal and basal cell layers. The stria forms endolymph and also contains a rich supply of blood vessels. (More? Inner Ear)
  • sulcus -
  • synostotically - anatomically normally separate skeletal bones fused together. (More? Middle Ear)
  • tectorial membrane - within the cochlea an extracellular matrix produced by interdental cells, that covers the sensory epithelial hair cells of the organ of corti. (More? Inner Ear)
  • alpha-tectorin and beta- (TECTA, TECTB) major non-collagenous protein component of the tectorial membrane forming a striated-sheet matrix. Synthesized as glycosylphosphatidylinositol-linked, membrane bound precursors.
  • temporal bone - (More? Middle Ear)
  • tensor tympani - (innervated by CN V mandibular nerve) one of the two muscles in the middle ear, contraction of this muscle pulls the malleus and tenses the tympanic membrane, dampening auditory ossicle movement. The muscle arises from auditory tube (cartilaginous portion) and is inserted into the malleus (manubrium near the root).
  • teratogens -
  • tonotopy - term describing the mapping along the tectorial membrane within the cochlea of the different sound frequencies. (More? Inner Ear)
  • tympanic membrane - (ear drum)
  • utricle -
  • vacuolization -
  • vesicle -
  • vestibular apparatus -
  • vestibular evoked myogenic potential (VEMP) test
  • vestibular ganglion - (Scarpa's ganglion) primary afferent vestibular neuron ganglion of the vestibular nerve. Located within the internal auditory meatus. (More? Inner Ear)
  • vestibular membrane - (Reissner's) extends from the spiral lamina to the outer wall and divides the cochlea into an upper scala vestibuli, a lower scala tympani. (More? Inner Ear)
  • Vestibulocochlear Nerve - Cranial Nerve VIII
  • Whirlin - A PDZ scaffold protein expressed in hair cells at the stereocilia tips, essential for the stereocilia elongation process. The DFNB31 gene mutations cause hearing loss in human and mouse. This protein can interact with membrane-associated guanylate kinase (MAGUK) protein, erythrocyte protein p55 (p55). (More? Inner Ear)
  • Wnt7a - signaling through the Wnt pathway regulates the development of hair cell unidirectional stereociliary bundle orientation. (More? Inner Ear)
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Cite this page: Hill, M.A. 2017 Embryology Hearing - Inner Ear Development. Retrieved October 24, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Hearing_-_Inner_Ear_Development

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