Hair cell differentiation becomes tissue specific by E9.5 in mouse inner ear

Neuroreport ◽  
2007 ◽  
Vol 18 (9) ◽  
pp. 841-844 ◽  
Author(s):  
Tatsunori Sakamoto ◽  
Juichi Ito ◽  
Raj K. Ladher
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Tissue Specific ◽  
Hair Cell Differentiation

Hes1 is a negative regulator of inner ear hair cell differentiation

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4551-4560 ◽  
Author(s):  
J.L. Zheng ◽  
J. Shou ◽  
F. Guillemot ◽  
R. Kageyama ◽  
W.Q. Gao
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Cell Fate ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Negative Regulator ◽  
Pcr Analysis ◽  
Loss Of Function ◽  
Hair Cell Differentiation

Hair cell fate determination in the inner ear has been shown to be controlled by specific genes. Recent loss-of-function and gain-of-function experiments have demonstrated that Math1, a mouse homolog of the Drosophila gene atonal, is essential for the production of hair cells. To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis. We report here that targeted deletion of Hes1 leads to formation of supernumerary hair cells in the cochlea and utricle of the inner ear. RT-PCR analysis shows that Hes1 is expressed in inner ear during hair cell differentiation and its expression is maintained in adulthood. In situ hybridization with late embryonic inner ear tissue reveals that Hes1 is expressed in supporting cells, but not hair cells, of the vestibular sensory epithelium. In the cochlea, Hes1 is selectively expressed in the greater epithelial ridge and lesser epithelial ridge regions which are adjacent to inner and outer hair cells. Co-transfection experiments in postnatal rat explant cultures show that overexpression of Hes1 prevents hair cell differentiation induced by Math1. Therefore Hes1 can negatively regulate hair cell differentiation by antagonizing Math1. These results suggest that a balance between Math1 and negative regulators such as Hes1 is crucial for the production of an appropriate number of inner ear hair cells.

scholarly journals The deltaA gene of zebrafish mediates lateral inhibition of hair cells in the inner ear and is regulated by pax2.1

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5669-5678 ◽  
Author(s):  
B.B. Riley ◽  
M. Chiang ◽  
L. Farmer ◽  
R. Heck
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Cell Fate ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Fold Increase ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Hair Cell Differentiation

Recent studies of inner ear development suggest that hair cells and support cells arise within a common equivalence group by cell-cell interactions mediated by Delta and Notch proteins. We have extended these studies by analyzing the effects of a mutant allele of the zebrafish deltaA gene, deltaA(dx2), which encodes a dominant-negative protein. deltaA(dx2/dx2)homozygous mutants develop with a 5- to 6-fold excess of hair cells and a severe deficiency of support cells. In addition, deltaA(dx2/dx2) mutants show an increased number of cells expressing pax2.1 in regions where hair cells are normally produced. Immunohistological analysis of wild-type and deltaA(dx2/dx2) mutant embryos confirmed that pax2.1 is expressed during the initial stages of hair cell differentiation and is later maintained at high levels in mature hair cells. In contrast, pax2.1 is not expressed in support cells. To address the function of pax2.1, we analyzed hair cell differentiation in no isthmus mutant embryos, which are deficient for pax2.1 function. no isthmus mutant embryos develop with approximately twice the normal number of hair cells. This neurogenic defect correlates with reduced levels of expression of deltaA and deltaD in the hair cells in no isthmus mutants. Analysis of deltaA(dx2/dx2); no isthmus double mutants showed that no isthmus suppresses the deltaA(dx2) phenotype, probably by reducing levels of the dominant-negative mutant protein. This interpretation was supported by analysis of T(msxB)(b220), a deletion that removes the deltaA locus. Reducing the dose of deltaA(dx2) by generating deltaA(dx2)/T(msxB)(b220)trans-heterozygotes weakens the neurogenic effects of deltaA(dx2), whereas T(msxB)(b220) enhances the neurogenic defects of no isthmus. mind bomb, another strong neurogenic mutation that may disrupt reception of Delta signals, causes a 10-fold increase in hair cell production and is epistatic to both no isthmus and deltaA(dx2). These data indicate that deltaA expressed by hair cells normally prevents adjacent cells from adopting the same cell fate, and that pax2.1 is required for normal levels of Delta-mediated lateral inhibition.

scholarly journals Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear

2013 ◽  
Vol 381 (2) ◽  
pp. 401-410 ◽  
Author(s):  
Kurt T. Chonko ◽  
Israt Jahan ◽  
Jennifer Stone ◽  
Margaret C. Wright ◽  
Tomoyuki Fujiyama ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Embryonic Mouse ◽  
Hair Cell Differentiation
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