Delta-1 Is a Regulator of Neurogenesis in the Vertebrate Retina

In the retina, cell fate determination is thought to be regulated by a series of local cell–cell interactions. Evidence suggests that retinal precursors utilize Notch-mediated intercellular signaling to regulate their fates. However, the identity of the endogenous ligand and its role in the Notch-signaling pathway is not well understood. We have identified C-Delta-1 as the putative endogenous ligand for Notch, in the developing chick retina.C-Delta-1is coexpressed spatially and temporally withC-Notch-1and their expression is associated with the temporal aspects of cell birth in the developing retina. This suggests that Delta–Notch signaling is utilized to maintain progenitors in an uncommitted state and that a subtle fluctuation in this signaling helps to sort out competent cells during successive cell-fate determination. We have tested the latter possibility in the specification of the ganglion cells. In early stages of retinal development when ganglion cells are the predominant cells born, decreasingC-Delta-1expression with antisense oligonucleotides increases the proportion of RA4 antigen-expressing ganglion cells which are recruited predominantly in the periphery. Conversely, use of exogenousDrosophilaDelta leads to a decrease in the RA4 antigen-expressing ganglion cells. Our results suggest that C-Delta-1 activation of the Notch pathway regulates the specification of retinal neurons in general and of ganglion cells in particular.