期刊
DEVELOPMENTAL DYNAMICS
卷 238, 期 9, 页码 2163-2178出版社
WILEY
DOI: 10.1002/dvdy.21848
关键词
notch activity; delta-like; Dll1; Dll4; Dll3; Ascl1; Neurog2; Hes1; Hes5; Hes6; retinal development; mutual and lateral inhibition; molecular circuit
资金
- NRSA [F32 EY15631]
- NICHD [T32 HD007183]
- NIH [EY13475]
Delta gene expression in Drosophila is regulated by proneural basic helix-loop-helix (bHLH) transcription factors, such as acheate-scute. In vertebrates, multiple Delta-like and proneural bHLH genes are expressed during neurogenesis, especially in the retina. We recently uncovered a relationship between Acheate-scute like 1 (Ascl1), Delta-like genes, and Notch in chick retinal progenitors. Here, we report that mammalian retinal progenitors are also the primary source of Delta-like genes, likely signaling through Notch among themselves, while differentiating neurons expressed Jagged2. Ascl1 is coexpressed in Delta-like and Notch active progenitors, and required for normal Delta-like gene expression and Notch signaling. We also reveal a role for Ascl1 in the regulation of Hes6, a proneurogenic factor that inhibits Notch signaling to promote neural rather than glial differentiation. Thus, these results suggest a molecular mechanism whereby attenuated Notch levels coupled with reduced proneurogenic activity in progenitors leads to increased gliogenesis and decreased neurogenesis in the Ascl1-deficient retina. Developmental Dynamics 238:2163-2178, 2009. (C) 2009 Wiley-Liss, Inc.
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