The retina is a favorite model for studying determination and differentiation in the central nervous system because of its ready accessibility, diversity of cell types and regular organization. Many molecules which act as potential inducers of cell fate have been identified by exposing progenitors to them and assaying their differentiation. In addition, heterochronic transplants demonstrate that regulation of cellular competence (i.e. the ability of progenitors to respond to inducers) plays an important role in differentiation. The neurogenic genes Delta and Notch acting as ligand and receptor, respectively, play a role in regulating cell competence by normally inhibiting progenitors from differentiating. Misexpression of an activated form of Notch 'freezes' progenitors in an undifferentiated, neuroepithelial state. Conversely, progenitors failing to be inhibited, either by their own overexpression of Delta, or by a dominant-negative Delta construct which blocks signaling, adopt the earliest fates generated in the retina (i.e. cones and ganglion cells). We suggest that retinal progenitors use lateral inhibition mediated by Delta-Notch to regulate their competence to respond to inductive cues in a changing environment. Such signaling is essential for formation of the proper cell types in appropriate numbers at the right stage of development to make functional circuits.
Copyright 1998 Academic Press.