Talk:Hearing - Inner Ear Development - Revision history

Z8600021 at 01:19, 19 Mayıs 2020

2020-05-19T01:19:35Z

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 Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgfβr1 is identified as being expressed in lateral progenitor cells and a Tgfβr1 antagonist inhibits OHC development. These results provide insights regarding cochlear development and demonstrate the potential value and application of this data set.
 PMCID: PMC7221106 DOI: 10.1038/s41467-020-16113-y
 ==2019==

Z8600021 at 01:15, 19 Mayıs 2020

2020-05-19T01:15:33Z

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			==2020==

			{{#pmid:32404924}}

			'''Characterization of the development of the mouse cochlear epithelium at the single cell level'''

			Mammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgfβr1 is identified as being expressed in lateral progenitor cells and a Tgfβr1 antagonist inhibits OHC development. These results provide insights regarding cochlear development and demonstrate the potential value and application of this data set.
			PMCID: PMC7221106 DOI: 10.1038/s41467-020-16113-y

	==2019==		==2019==

Z8600021 at 22:49, 19 November 2019

2019-11-19T22:49:09Z

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			==2019==
			{{#pmid:31570588}}

			Abstract
			Development of multicellular organs requires the coordination of cell differentiation and patterning. Critical for sound detection, the mammalian organ of Corti contains functional units arranged tonotopically along the cochlear turns. Each unit consists of sensory hair cells intercalated by nonsensory supporting cells, both specified and radially patterned with exquisite precision during embryonic development. However, how cell identity and radial patterning are jointly controlled is poorly understood. Here we show that β-catenin is required for specification of hair cell and supporting cell subtypes and radial patterning of the cochlea in vivo. In 2 mouse models of conditional β-catenin deletion, early specification of Myosin7-expressing hair cells and Prox1-positive supporting cells was preserved. While β-catenin-deficient cochleae expressed FGF8 and FGFR3, both of which are essential for pillar cell specification, the radial patterning of organ of Corti was disrupted, revealed by aberrant expression of cadherins and the pillar cell markers P75 and Lgr6. Moreover, β-catenin ablation caused duplication of FGF8-positive inner hair cells and reduction of outer hair cells without affecting the overall hair cell density. In contrast, in another transgenic model with suppressed transcriptional activity of β-catenin but preserved cell adhesion function, both specification and radial patterning of the organ of Corti were intact. Our study reveals specific functions of β-catenin in governing cell identity and patterning mediated through cell adhesion in the developing cochlea.
			KEYWORDS:
			Wnt signaling; cell adhesion; cochlea; development; hair cell
			PMID: 31570588 PMCID: PMC6800344 [Available on 2020-03-30] DOI: 10.1073/pnas.1910223116

	==2018==		==2018==

Z8600021 at 02:13, 6 September 2018

2018-09-06T02:13:33Z

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	PMID: 30108474 PMCID: PMC6079228 DOI: 10.3389/fnins.2018.00501		PMID: 30108474 PMCID: PMC6079228 DOI: 10.3389/fnins.2018.00501


			Copyright © 2018 Glueckert, Johnson Chacko, Schmidbauer, Potrusil, Pechriggl, Hoermann, Brenner, Reka, Schrott-Fischer and Handschuh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

	===Formation of the Periotic Space During the Early Fetal Period in Humans===		===Formation of the Periotic Space During the Early Fetal Period in Humans===

Z8600021 at 02:12, 6 September 2018

2018-09-06T02:12:44Z

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	==2018==		==2018==

			===Visualization of the Membranous Labyrinth and Nerve Fiber Pathways in Human and Animal Inner Ears Using MicroCT Imaging===
			{{#pmid:30108474}}

			Glueckert R1,2, Johnson Chacko L1, Schmidbauer D1,3, Potrusil T1, Pechriggl EJ4, Hoermann R4, Brenner E4, Reka A1, Schrott-Fischer A1, Handschuh S5.
			Author information
			Abstract
			Design and implantation of bionic implants for restoring impaired hair cell function relies on accurate knowledge about the microanatomy and nerve fiber pathways of the human inner ear and its variation. Non-destructive isotropic imaging of soft tissues of the inner ear with lab-based microscopic X-ray computed tomography (microCT) offers high resolution but requires contrast enhancement using compounds with high X-ray attenuation. We evaluated different contrast enhancement techniques in mice, cat, and human temporal bones to differentially visualize the membranous labyrinth, sensory epithelia, and their innervating nerves together with the facial nerve and middle ear. Lugol's iodine potassium iodine (I2KI) gave high soft tissue contrast in ossified specimens but failed to provide unambiguous identification of smaller nerve fiber bundles inside small bony canals. Fixation or post-fixation with osmium tetroxide followed by decalcification in EDTA provided superior contrast for nerve fibers and membranous structures. We processed 50 human temporal bones and acquired microCT scans with 15 μm voxel size. Subsequently we segmented sensorineural structures and the endolymphatic compartment for 3D representations to serve for morphometric variation analysis. We tested higher resolution image acquisition down to 3.0 μm voxel size in human and 0.5 μm in mice, which provided a unique level of detail and enabled us to visualize single neurons and hair cells in the mouse inner ear, which could offer an alternative quantitative analysis of cell numbers in smaller animals. Bigger ossified human temporal bones comprising the middle ear and mastoid bone can be contrasted with I2KI and imaged in toto at 25 μm voxel size. These data are suitable for surgical planning for electrode prototype placements. A preliminary assessment of geometric changes through tissue processing resulted in 1.6% volume increase caused during decalcification by EDTA and 0.5% volume increase caused by partial dehydration to 70% ethanol, which proved to be the best mounting medium for microCT image acquisition.
			KEYWORDS:
			endolymph; inner ear implants; membranous labyrinth; microCT; microanatomy; nerve fiber tracking; non-destructive imaging; perilymph
			PMID: 30108474 PMCID: PMC6079228 DOI: 10.3389/fnins.2018.00501


	===Formation of the Periotic Space During the Early Fetal Period in Humans===		===Formation of the Periotic Space During the Early Fetal Period in Humans===

Z8600021 at 03:32, 8 Mayıs 2018

2018-05-08T03:32:45Z

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	==2017==		==2017==

			===Autophagy in the Vertebrate Inner Ear===

			Front Cell Dev Biol. 2017 May 26;5:56. doi: 10.3389/fcell.2017.00056. eCollection 2017.

			Magariños M1,2,3, Pulido S1,2, Aburto MR1, de Iriarte Rodríguez R1, Varela-Nieto I1,2,4.

			Abstract

			Autophagy is a conserved catabolic process that results in the lysosomal degradation of cell components. During development, autophagy is associated with tissue and organ remodeling, and under physiological conditions it is tightly regulated as it plays a housekeeping role in removing misfolded proteins and damaged organelles. The vertebrate inner ear is a complex sensory organ responsible for the perception of sound and for balance. Cell survival, death and proliferation, as well as cell fate specification and differentiation, are processes that are strictly coordinated during the development of the inner ear in order to generate the more than a dozen specialized cell types that constitute this structure. Here, we review the existing evidence that implicates autophagy in the generation of the vertebrate inner ear. At early stages of chicken otic development, inhibiting autophagy impairs neurogenesis and causes aberrant otocyst morphogenesis. Autophagy provides energy for the clearing of dying cells and it favors neuronal differentiation. Moreover, autophagy is required for proper vestibular development in the mouse inner ear. The autophagy-related genes Becn1, Atg4g, Atg5, and Atg9, are expressed in the inner ear from late developmental stages to adulthood, and Atg4b mutants show impaired vestibular behavior associated to defects in otoconial biogenesis that are also common to Atg5 mutants. Autophagic flux appears to be age-regulated, augmenting from perinatal stages to young adulthood in mice. This up-regulation is concomitant with the functional maturation of the hearing receptor. Hence, autophagy can be considered an intracellular pathway fundamental for in vertebrate inner ear development and maturation.
			KEYWORDS:
			Atg4; Atg5; Beclin-1; LC3; cochlea; otic development; vestibular system
			PMID: 28603711 PMCID: PMC5445191 DOI: 10.3389/fcell.2017.00056

	===Role of BDNF and neurotrophic receptors in human inner ear development===		===Role of BDNF and neurotrophic receptors in human inner ear development===

Z8600021 at 01:51, 6 April 2018

2018-04-06T01:51:56Z

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	human early fetus; membranous labyrinth; otic capsule; periotic space; three-dimensional kinetics		human early fetus; membranous labyrinth; otic capsule; periotic space; three-dimensional kinetics
	PMID: 29293291 DOI: 10.1002/ar.23764		PMID: 29293291 DOI: 10.1002/ar.23764

			===Developmental profiling of microRNAs in the human embryonic inner ear===

			PLoS One. 2018 Jan 26;13(1):e0191452. doi: 10.1371/journal.pone.0191452. eCollection 2018.

			Chadly DM1, Best J1, Ran C1, Bruska M2, Woźniak W2, Kempisty B2, Schwartz M3, LaFleur B3, Kerns BJ3, Kessler JA4, Matsuoka AJ1,5,6.

			Abstract

			Due to the extreme inaccessibility of fetal human inner ear tissue, defining of the microRNAs (miRNAs) that regulate development of the inner ear has relied on animal tissue. In the present study, we performed the first miRNA sequencing of otic precursors in human specimens. Using HTG miRNA Whole Transcriptome assays, we examined miRNA expression in the cochleovestibular ganglion (CVG), neural crest (NC), and otic vesicle (OV) from paraffin embedded (FFPE) human specimens in the Carnegie developmental stages 13-15. We found that in human embryonic tissues, there are different patterns of miRNA expression in the CVG, NC and OV. In particular, members of the miR-183 family (miR-96, miR-182, and miR-183) are differentially expressed in the CVG compared to NC and OV at Carnegie developmental stage 13. We further identified transcription factors that are differentially targeted in the CVG compared to the other tissues from stages 13-15, and we performed gene set enrichment analyses to determine differentially regulated pathways that are relevant to CVG development in humans. These findings not only provide insight into the mechanisms governing the development of the human inner ear, but also identify potential signaling pathways for promoting regeneration of the spiral ganglion and other components of the inner ear.
			PMID: 29373586 PMCID: PMC5786302 DOI: 10.1371/journal.pone.0191452

Z8600021 at 02:40, 11 March 2018

2018-03-11T02:40:14Z

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			==2018==

			===Formation of the Periotic Space During the Early Fetal Period in Humans===

			Anat Rec (Hoboken). 2018 Apr;301(4):563-570. doi: 10.1002/ar.23764. Epub 2018 Jan 18.

			Ishikawa A1, Ohtsuki S1, Yamada S1,2, Uwabe C2, Imai H3, Matsuda T3, Takakuwa T1.

			Abstract

			The inner ear is a very complicated structure, composed of a bony labyrinth (otic capsule; OC), membranous labyrinth, with a space between them, named the periotic labyrinth or periotic space. We investigated how periotic tissue fluid spaces covered the membranous labyrinth three-dimensionally, leading to formation of the periotic labyrinth encapsulated in the OC during human fetal development. Digital data sets from magnetic resonance images and phase-contrast X-ray tomography images of 24 inner ear organs from 24 human fetuses from the Kyoto Collection (fetuses in trimesters 1 and 2; crown-rump length: 14.4-197 mm) were analyzed. The membranous labyrinth was morphologically differentiated in samples at the end of the embryonic period (Carnegie stage 23), and had grown linearly to more than eight times in size during the observation period. The periotic space was first detected at the 35-mm samples, around the vestibule and basal turn of the cochlea, which elongated rapidly to the tip of the cochlea and semicircular ducts, successively, and almost covered the membranous labyrinth at the 115-mm CRL stage or later. In those samples, several ossification centers were detected around the space. This article thus demonstrated that formation of the membranous labyrinth, periotic space (labyrinth), and ossification of the OC occurs successively, according to an intricate timetable. Anat Rec, 301:563-570, 2018.
			© 2018 Wiley Periodicals, Inc.
			KEYWORDS:
			human early fetus; membranous labyrinth; otic capsule; periotic space; three-dimensional kinetics
			PMID: 29293291 DOI: 10.1002/ar.23764


	==2017==		==2017==

Z8600021 at 22:48, 2 November 2017

2017-11-02T22:48:11Z

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			==2017==

			===Role of BDNF and neurotrophic receptors in human inner ear development===
			Cell Tissue Res. 2017 Sep 19. doi: 10.1007/s00441-017-2686-9. [Epub ahead of print]

			Johnson Chacko L1, Blumer MJF2, Pechriggl E2, Rask-Andersen H3, Dietl W1, Haim A4, Fritsch H2, Glueckert R1,5, Dudas J6, Schrott-Fischer A1.

			Abstract

			The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.
			KEYWORDS:
			BDNF; Human; In situ hybridization; Inner ear; Neurotrophin receptors

			PMID: 28924861 DOI: 10.1007/s00441-017-2686-9

	==2016==		==2016==

Z8600021 at 03:08, 26 Mayıs 2016

2016-05-26T03:08:09Z

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	==2016==		==2016==
			===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 Jun 1;414(1):72-84. doi: 10.1016/j.ydbio.2016.03.027. Epub 2016 Apr 14.

			Gu R1, Brown RM 2nd2, Hsu CW3, Cai T1, Crowder AL1, Piazza VG3, Vadakkan TJ3, Dickinson ME4, Groves AK5.

			Abstract

			The transcription factor Sox2 is both necessary and sufficient for the generation of sensory regions of the inner ear. It regulates expression of the Notch ligand Jag1 in prosensory progenitors, which signal to neighboring cells to up-regulate Sox2 and sustain prosensory identity. However, the expression pattern of Sox2 in the early inner ear is very broad, suggesting that Sox2-expressing progenitors form a wide variety of cell types in addition to generating the sensory regions of the ear. We used Sox2-CreER mice to follow the fates of Sox2-expressing cells at different stages in ear development. 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.
			Copyright © 2016 Elsevier Inc. All rights reserved.
			KEYWORDS:
			Cochlea; Inner ear; Organ of Corti; Otocyst; Sensory; Sox2
			PMID 27090805

	===Temporal coupling between specifications of neuronal and macular fates of the inner ear===		===Temporal coupling between specifications of neuronal and macular fates of the inner ear===