Acheate-scute like 1 (Ascl1) Is Required for Normal Delta-like (Dll) Gene Expression and Notch Signaling During Retinal Development

作者：Nelson Branden R^*; Hartman Byron H; Ray Catherine A; Hayashi Toshinori; Bermingham McDonogh Olivia; Reh Thomas A

来源：Developmental Dynamics, 2009, 238(9): 2163-2178.

DOI：10.1002/dvdy.21848

• notch activity
• delta-like
• Dll1
• Dll4
• Dll3
• Ascl1
• Neurog2
• Hes1
• Hes5
• Hes6
• retinal development
• mutual and lateral inhibition
• molecular circuit

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.

• 出版日期2009-9