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Keywords:

  • Notch activity, Delta-like, Dll1;
  • Dll4;
  • Ascl1;
  • Neurog2;
  • Atoh7;
  • NeuroD4;
  • Hes1;
  • Hes5;
  • retinogenesis;
  • stem cell;
  • progenitor cell;
  • ciliary marginal zone;
  • mutual inhibition;
  • lateral inhibition

Abstract

Notch signaling in the retina maintains a pool of progenitor cells throughout retinogenesis. However, two Notch-ligands from the Delta-like gene family, Dll1 and Dll4, are present in the developing retina. To understand their relationship, we characterized Dll1 and Dll4 expression with respect to proliferating progenitor cells and newborn neurons in the chick retina. Dll4 matched the pattern of neural differentiation. By contrast, Dll1 was primarily expressed in progenitor cells. We compared Dll1 and Dll4 kinetic profiles with that of the transiently up-regulated cascade of proneural basic helix–loop–helix (bHLH) genes after synchronized progenitor cell differentiation, which suggested a potential role for Ascl1 in the regulation of Delta-like genes. Gain-of-function assays demonstrate that Ascl1 does influence Delta-like gene expression and Notch signaling activity. These data suggest that multiple sources of Notch signaling from newborn neurons and progenitors themselves coordinate retinal histogenesis. Developmental Dynamics 237:1565–1580, 2008. © 2008 Wiley-Liss, Inc.