Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears

Zheng, Jie; Gao, Wei

doi:10.1038/75753

Cited by 716 publications

(504 citation statements)

References 43 publications

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“…The bHLH transcription factor ATOH1 (Math-1) appears to act at a later point in this pathway, but is also essential for hair cell differentiation and potentially for determination of support cells (Bermingham et al, 1999;Woods et al, 2004). Ectopic expression of ATOH1 has been shown to induce the differentiation of hair cells de novo in the embryonic and adult inner ear (Izumikawa et al, 2005;Kawamoto et al, 2003;Woods et al, 2004;Zheng and Gao, 2000). Other members of the bHLH family, including NGN1 and NEUROD2, play a central role in sensoriepithelial and cochleovestibular ganglion development (Kim et al, 2001;Liu et al, 2000;Ma et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

“…At this stage of inner ear development, cells in the SOX2-expressing region of the GER are undergoing cellular rearrangements that eventually give rise to the inner sulcus. GER cells are believed to be relatively undifferentiated, as demonstrated by their ability to transdifferentiate into hair cells with ectopic expression of ATOH1 (Woods et al, 2004;Zheng and Gao, 2000). At postnatal day 2, ATOH1, LHX3 and MYO6 are detectable along the entire axis of the cochlea in inner and outer hair cells ( Figure 3E-P).…”

Section: Early Postnatal Maturationmentioning

confidence: 98%

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Expression of LHX3 and SOX2 during mouse inner ear development

Hume

Bratt

Oesterle

2007

Gene Expression Patterns

136

140

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A cascade of transcription factors is believed to regulate the coordinate differentiation of primordial inner ear cells into the subtypes of hair cells and supporting cells. While candidate genes involved in this process have been identified, the temporal and spatial patterns of expression of many of these have not been carefully described during the extended period of inner ear development and functional maturation. We systematically examined the expression of two such transcription factors, LHX3 and SOX2, from the time of hair cell terminal mitoses into adulthood. We show that LHX3 is expressed specifically in auditory and vestibular hair cells soon after terminal mitoses and persists into the adult in vestibular hair cells. While SOX2 expression is widespread in the inner ear sensory epithelia prior to hair cell differentiation, it has a unique pattern of expression in the mature auditory and vestibular organs.

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Section: Resultsmentioning

confidence: 99%

Section: Early Postnatal Maturationmentioning

confidence: 98%

Expression of LHX3 and SOX2 during mouse inner ear development

Hume

Bratt

Oesterle

2007

Gene Expression Patterns

136

140

View full text Add to dashboard Cite

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“…It is known that neurotrophic factors are important for hair cell development (Chabbert et al 2003), and a recent report indicates that epidermal growth factor (EGF) may be required to induce formation of new hair cells (Doetzlhofer et al 2004). The formation of new hair cells may also require overexpression of Math1, a transcription factor downstream in the EGF pathway that is essential for hair cell development (Zheng and Gao 2000;Woods et al 2004). The regeneration of mammalian hair cells in vivo and resultant recovery of auditory function by overexpression of Math1 (Izumikawa et al 2005) supports this combined therapeutic approach.…”

Section: Discussionmentioning

confidence: 99%

Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

Hildebrand

Dahl

Hardman

et al. 2005

JARO

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The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment.

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“…Several groups have successfully generated ectopic HCs by transfecting cochlear explants or by in utero electroporation with Atoh1 under the control of a constitutively active promoter (Zheng and Gao 2000;Gubbels et al 2008). Epithelial cells of the greater epithelial ridge readily take on a HC fate demonstrating that, even after HC differentiation has started, surrounding cells of the cochlea retain the competence to take on a sensory identity (Zheng and Gao 2000).…”

Section: Atoh1 and Auditory Hair Cellsmentioning

confidence: 99%

Atoh1, an Essential Transcription Factor in Neurogenesis and Intestinal and Inner Ear Development: Function, Regulation, and Context Dependency

Mulvaney

Dabdoub

2012

JARO

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Atoh1 (also known as Math1, Hath1, and Cath1 in mouse, human, and chicken, respectively) is a proneural basic helix-loop-helix (bHLH) transcription factor that is required in a variety of developmental contexts. Atoh1 is involved in differentiation of neurons, secretory cells in the gut, and mechanoreceptors including auditory hair cells. Together with the two closely related bHLH genes, Neurog1 and NeuroD1, Atoh1 regulates neurosensory development in the ear as well as neurogenesis in the cerebellum. Atoh1 activity in the cochlea is both necessary and sufficient to drive auditory hair cell differentiation, in keeping with its known role as a regulator of various genes that are markers of terminal differentiation. Atoh1 is known in other fields as an oncogene and a tumor suppressor involved in regulation of cell cycle control and apoptosis. Aberrant Atoh1 activity in adult tissue is implicated in cancer progression, specifically in medullablastoma and adenomatous polyposis carcinoma. We demonstrate through protein sequence comparison that Atoh1 contains conserved phosphorylation sites outside the bHLH domain, which may allow regulation through post-translational modification. With such diverse roles, tight regulation of Atoh1 at both the transcriptional and protein level is essential.

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Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears

Cited by 716 publications

References 43 publications

Expression of LHX3 and SOX2 during mouse inner ear development

Expression of LHX3 and SOX2 during mouse inner ear development

Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

Atoh1, an Essential Transcription Factor in Neurogenesis and Intestinal and Inner Ear Development: Function, Regulation, and Context Dependency

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