Delta-1 is a regulator of neurogenesis in the vertebrate retina

Dev Biol. 1997 May 1;185(1):92-103. doi: 10.1006/dbio.1997.8546.

Abstract

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-1 is coexpressed spatially and temporally with C-Notch-1 and 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, decreasing C-Delta-1 expression with antisense oligonucleotides increases the proportion of RA4 antigen-expressing ganglion cells which are recruited predominantly in the periphery. Conversely, use of exogenous Drosophila Delta 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chick Embryo
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Morphogenesis
  • Nervous System / embryology*
  • Neurons
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Messenger / genetics
  • Receptor, Notch1
  • Receptors, Cell Surface*
  • Retina / cytology
  • Retina / drug effects
  • Retina / embryology*
  • Transcription Factors*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Transcription Factors
  • delta protein