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COUP-TFI controls Notch regulation of hair cell and support cell differentiation.
- Source :
- Development (09501991); Sep2006, Vol. 133 Issue 18, p18-18, 1p
- Publication Year :
- 2006
-
Abstract
- The orphan nuclear receptor COUP-TFI (Nr2f1) regulates many aspects of mammalian development, but little is known about its role in cochlear hair cell and Deiter's support cell development. The COUP-TFI knockout (COUP-TFI<superscript>-/-</superscript>) has a significant increase in hair cell (HC) number in the mid-to-apical turns. The total number of hair cells is not increased over wild type, perhaps because of displaced hair cells and a shortened cochlear duct. This implicates a defect of convergent-extension in the COUP-TFI<superscript>-/-</superscript> duct. In addition, excess proliferation in the COUP-TFI<superscript>-/-</superscript> sensory epithelium indicates that the origin of the extra HCs in the apex is complex. Because loss-of-function studies of Notch signaling components have similar phenotypes, we investigated Notch regulation of hair cell differentiation in COUP-TFI<superscript>-/-</superscript> mice and confirmed misregulation of Notch signaling components, including Jag1, Hes5 and in a manner consistent with reduced Notch signaling, and correlated with increases in hair cell and support cell differentiation. The disruption of Notch signaling by a γ-secretase inhibitor in an in vitro organ culture system of wild-type cochleae resulted in a reduction in expression of the Notch target gene Hes5 and an increase in hair cell differentiation. Importantly, inhibition of Notch activity resulted in a greater increase in hair cell differentiation in COUP-TFI<superscript>-/-</superscript> cochlear cultures than in wild-type cultures, suggesting a hypersensitivity to Notch inactivation in COUP-TFI<superscript>-/-</superscript> cochlea, particularly at the apical turn. Thus, we present evidence that reduced Notch signaling contributes to increases in hair cell and support cell differentiation in COUP-TFI<superscript>-/-</superscript> mice, and suggest that COUP-TFI is required for Notch regulation of hair cell and support cell differentiation. [ABSTRACT FROM AUTHOR]
- Subjects :
- MAMMALS
HAIR cells
CELLS
EPITHELIUM
CELL differentiation
Subjects
Details
- Language :
- English
- ISSN :
- 09501991
- Volume :
- 133
- Issue :
- 18
- Database :
- Complementary Index
- Journal :
- Development (09501991)
- Publication Type :
- Academic Journal
- Accession number :
- 22402235
- Full Text :
- https://doi.org/10.1242/dev.02536