<i>Math1</i>
            : An Essential Gene for the Generation of Inner Ear Hair Cells

Bermingham, Nessan A.; Hassan, Bassem A.; Price, Steven D.; Vollrath, Melissa A.; Ben‐Arie, Nissim; Eatock, Ruth Anne; Bellen, Hugo J.; Lysakowski, Anna; Zoghbi, Huda Y.

doi:10.1126/science.284.5421.1837

Cited by 1,027 publications

(999 citation statements)

References 25 publications

Supporting

Mentioning

944

Contrasting

Unclassified

Order By: Relevance

“…Alternatively, Hes6 is an immediate early hair cell gene activated by a Math1-initiated hair cell differentiation program. To determine whether Hes6 expression depends on Math1, we examined the expression of Hes6 in Math1 null animals (Bermingham et al, 1999). At E14.5, Hes6 expression was detected in columns of hair cell precursors in wild-type littermates (Fig.…”

Section: Hes6 Expression In Sensory Hair Cells Depends On Math1mentioning

confidence: 99%

“…The molecular mechanisms underlying the development of the sensory lineage and the patterning of the or-gan of Corti have been studied extensively (Adam et al, 1998;Haddon et al, 1998;Lewis et al, 1998;Lewis, 1998;Bermingham et al, 1999;Lanford et al, 1999Lanford et al, , 2000Morrison et al, 1999;Riley et al, 1999;Eddison et al, 2000;Zhang et al, 2000;Zine et al, 2000Zine et al, , 2001Tsai et al, 2001;Bryant et al, 2002;Chen et al, 2002;Fekete and Wu, 2002;Radde-Gallwitz et al, 2004;Woods et al, 2004;Daudet and Lewis, 2005;Kiernan et al, 2005a,b;Matei et al, 2005). In particular, two classes of basic helix-loop-helix (bHLH)-containing factors, namely the positively and negatively acting transcription factors, have been shown to play essential roles in the differentiation of sensory hair cells and the patterning of the sensory mosaic in the organ of Corti (Bermingham et al, 1999;Zine et al, 2000Zine et al, , 2001Chen et al, 2002;Woods et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, two classes of basic helix-loop-helix (bHLH)-containing factors, namely the positively and negatively acting transcription factors, have been shown to play essential roles in the differentiation of sensory hair cells and the patterning of the sensory mosaic in the organ of Corti (Bermingham et al, 1999;Zine et al, 2000Zine et al, , 2001Chen et al, 2002;Woods et al, 2004). Math1, a mouse homolog of the Drosophila proneural bHLH gene Atonal, also known as Atoh1 (Atonal homolog 1), is up-regulated within the sensory precursor domain of the cochlea around E13.5-E14.5 (Chen et al, 2002;Woods et al, 2004;Kiernan et al, 2005a;Matei et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Basic helix–loop–helix gene Hes6 delineates the sensory hair cell lineage in the inner ear

et al. 2006

View full text Add to dashboard Cite

The basic helix-loop-helix (bHLH) gene Hes6 is known to promote neural differentiation in vitro. Here, we report the expression and functional studies of Hes6 in the inner ear. The expression of Hes6 appears to be parallel to that of Math1 (also known as Atoh1), a bHLH gene necessary and sufficient for hair cell differentiation. Hes6 is expressed initially in the presumptive hair cell precursors in the cochlea. Subsequently, the expression of Hes6 is restricted to morphologically differentiated hair cells. Similarly, the expression of Hes6 in the vestibule is in the hair cell lineage. Hes6 is dispensable for hair cell differentiation, and its expression in inner ear hair cells is abolished in the Math1-null animals. Furthermore, the introduction of Hes6 into the cochlea in vitro is not sufficient to promote sensory or neuronal differentiation. Therefore, Hes6 is downstream of Math1 and its expression in the inner ear delineates the sensory lineage. However, the role of Hes6 in the inner ear remains elusive.

show abstract

Section: Hes6 Expression In Sensory Hair Cells Depends On Math1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Basic helix–loop–helix gene Hes6 delineates the sensory hair cell lineage in the inner ear

et al. 2006

View full text Add to dashboard Cite

show abstract

“…In Jagged2 deficient mice, this inhibition is affected, resulting in the increase of hair cells at the expense of support cells [22]. This Jagged2-dependent Notch activation probably targets to the bHLH gene Math1, which is essential for generation of hair cells [23,24]. Thus, in the inner ear the pathway Jagged2-Notch-RBPJ-Hes1/Hes5-|Math1 regulates generation of hair cells and support cells, and abnormality of this pathway leads to the lack of one of the two cell types.…”

Section: Inner Ear Development and The Notch Pathwaymentioning

confidence: 99%

The Notch-Hes pathway in mammalian neural development

1999

View full text Add to dashboard Cite

A wide variety of neurons and glial cells differentiate from common precursor cells in the developing nervous system. During this process, Notch-mediated cell-cell interaction is essential for maintenance of dividing cells and subsequent generation of cell type diversity. Activation of Notch inhibits cellular differentiation, and abnormality of the Notch pathway leads to premature neuronal differentiation, the lack of some cell types, and severe defects of tissue morphogenesis. Recent data demonstrate that Notch fails to inhibit cellular differentiation in the absence of the bHLH genes Hes1 and Hes5, which functionally antagonize the neuronal bHLH genes such as Mash1. These results indicate that the two Hes genes are essential effectors for the Notch pathway and that neuronal differentiation is controlled by the pathway "Notch-Hes1/ Hes5-|Mash1".

show abstract

“…Atoh1, a transcription factor belonging to the family of basic helix-loop-helix (bHLH)-containing proteins, plays a critical role for hair cell differentiation and survival during development and adulthood [15,17,18]. The Atoh1 -CKO mouse self-terminates expression of Atoh1 in hair cells around birth using an Atoh1 enhancer to drive cre to conditionally delete the floxed Atoh1 .…”

Section: Introductionmentioning

confidence: 99%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.

show abstract

Math1 : An Essential Gene for the Generation of Inner Ear Hair Cells

Cited by 1,027 publications

References 25 publications

Basic helix–loop–helix gene Hes6 delineates the sensory hair cell lineage in the inner ear

Basic helix–loop–helix gene Hes6 delineates the sensory hair cell lineage in the inner ear

The Notch-Hes pathway in mammalian neural development

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Contact Info

Product

Resources

About