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Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development
Author(s) -
Nelson Branden R.,
Hartman Byron H.,
Ray Catherine A.,
Hayashi Toshinori,
BerminghamMcDonogh Olivia,
Reh Thomas A.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21848
Subject(s) - biology , proneural genes , notch signaling pathway , neurogenesis , gliogenesis , microbiology and biotechnology , muller glia , cell fate determination , progenitor cell , transcription factor , hes3 signaling axis , genetics , signal transduction , gene , stem cell
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. © 2009 Wiley‐Liss, Inc.