Neurod1 Suppresses Hair Cell Differentiation in Ear Ganglia and Regulates Hair Cell Subtype Development in the Cochlea

Jahan, Israt; Pan, Ning; Kersigo, Jennifer; Fritzsch, Bernd

doi:10.1371/journal.pone.0011661

Cited by 119 publications

(207 citation statements)

References 75 publications

(167 reference statements)

Supporting

Mentioning

192

Contrasting

Unclassified

Order By: Relevance

“…This spatiotemporal pattern closely matches that of hair cell differentiation in the cochlear duct, raising the hypothesis that Shh regulates the timing of hair cell differentiation. This is indirectly supported by the finding that loss of the spiral ganglia in Neurod1 −/− and Neurog1 −/− mice leads to premature cell cycle exit and hair cell differentiation in the cochlear duct (Jahan et al, 2010;Matei et al, 2005).…”

Section: Shh Signalingmentioning

confidence: 75%

Sensory hair cell development and regeneration: similarities and differences

et al. 2015

View full text Add to dashboard Cite

Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration.

show abstract

Section: Shh Signalingmentioning

confidence: 75%

Sensory hair cell development and regeneration: similarities and differences

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Atoh1, Sox2, β-catenin, Hfn1a, and Cdx2 upregulate Atoh1 expression (Helms et al 2000;Ebert et al 2003;Gazit et al 2004;Mutoh et al 2006;D'Angelo et al 2010;Shi et al 2010;Neves et al 2011). Hes1, Hes5, Sox2, Hic1, Ngn1, NeuroD1, and Zic1 repress Atoh1 at the level of transcription (Akazawa et al 1995;Gowan et al 2001;Ebert et al 2003;Qian et al 2006;Briggs et al 2008;Dabdoub et al 2008;Pan et al 2009;Jahan et al 2010). Intriguingly, Sox2 has the ability to both upregulate and downregulate Atoh1 depending on context (Dabdoub et al 2008;Neves et al 2011).…”

Section: Genetic Regulationmentioning

confidence: 99%

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

Mulvaney

Dabdoub

2012

JARO

View full text Add to dashboard Cite

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.

show abstract

“…After, the lipophilic dye tracing the same tissue of interest can then be analyzed using in situ hybridization, for analysis of gene transcription and can be subsequently analyzed using immunohistochemistry for protein distribution. The latter analysis can be supplemented by detailed histology which can add to the phenotype characterization 6 . This multifactorial analysis has the potential to gain new insights through correlative analysis within the same animal that may otherwise be improbable or at least in need of more extensive protocols and mouse breeding.…”

Section: Discussionmentioning

confidence: 99%

Combining Lipophilic dye, <em>in situ</em> Hybridization, Immunohistochemistry, and Histology

Duncan¹,

Kersigo²,

Gray³

et al. 2011

JoVE

Self Cite

View full text Add to dashboard Cite

Going beyond single gene function to cut deeper into gene regulatory networks requires multiple mutations combined in a single animal. Such analysis of two or more genes needs to be complemented with in situ hybridization of other genes, or immunohistochemistry of their proteins, both in whole mounted developing organs or sections for detailed resolution of the cellular and tissue expression alterations. Combining multiple gene alterations requires the use of cre or flipase to conditionally delete genes and avoid embryonic lethality. Required breeding schemes dramatically enhance effort and cost proportional to the number of genes mutated, with an outcome of very few animals with the full repertoire of genetic modifications desired. Amortizing the vast amount of effort and time to obtain these few precious specimens that are carrying multiple mutations necessitates tissue optimization. Moreover, investigating a single animal with multiple techniques makes it easier to correlate gene deletion defects with expression profiles. We have developed a technique to obtain a more thorough analysis of a given animal; with the ability to analyze several different histologically recognizable structures as well as gene and protein expression all from the same specimen in both whole mounted organs and sections. Although mice have been utilized to demonstrate the effectiveness of this technique it can be applied to a wide array of animals. To do this we combine lipophilic dye tracing, whole mount in situ hybridization, immunohistochemistry, and histology to extract the maximal possible amount of data. Video LinkThe video component of this article can be found at https://www.jove.com/video/2451/ Protocol Lipophilic Dye Injection Tissue Preparation:All tissue dissections and manipulations are carried out in animals fixed in 4% paraformaldehyde (PFA) in 0.1 M phosphate buffer (pH 7.4) by transcardial perfusion using peristaltic pumps with appropriately sized needles. Tissue can be stored in 4% PFA in the refrigerator for up to 6 months. All preparations and manipulations are conducted in 0.4 % or higher PFA until mounting with glycerol for imaging. This amount of PFA effectively eliminates RNases and preserves the RNA for in situ hybridization. Dye Storage:All dyes should be stored in a dark closed compartment to minimize air circulation and exposure to bright daylight, as they are photosensitive. To avoid cross contamination, a separate set of instruments should be used to handle each dye.1. First, an application site for the dye must be chosen and extraneous tissue extracted in order to visually confirm the chosen site, and access for placement of the dye. Choosing the application site is the most important step in this process. Choosing a good site to label the neuronal population under consideration and not extraneous structures can be challenging. The accuracy of the placement into a given tract under visual control in the dissecting scope requires a certain level of understanding of the neuroanatomy in question. Dye...

show abstract

Neurod1 Suppresses Hair Cell Differentiation in Ear Ganglia and Regulates Hair Cell Subtype Development in the Cochlea

Cited by 119 publications

References 75 publications

Sensory hair cell development and regeneration: similarities and differences

Sensory hair cell development and regeneration: similarities and differences

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

Combining Lipophilic dye, <em>in situ</em> Hybridization, Immunohistochemistry, and Histology

Contact Info

Product

Resources

About