VERTEBRATE RETINAL GANGLION-CELLS ARE SELECTED FROM COMPETENT PROGENITORS BY THE ACTION OF NOTCH

The first cells generated during development of the vertebrate retina are the ganglion cells, the projection neurons of the retina. Although they are one of the most intensively studied cell types within the ce ntral nervous system, little is known of the mechanisms that determine ganglion cell fate. We demonstrate that ganglion cells are selected f rom a large group of competent progenitors that comprise the majority of the early embryonic retina and that differentiation within this gro up is regulated by Notch. Notch activity in vivo was diminished using antisense oligonucleotides or augmented using a retrovirally transduce d constitutively active allele of Notch. The number of ganglion cells produced was inversely related to the level of Notch activity. In addi tion, the Notch ligand Delta inhibited retinal progenitors from differ entiating as ganglion cells to the same degree as did activated Notch in an in vitro assay. These results suggest a conserved strategy for n eurogenesis in the retina and describe a versatile in vitro and in viv o system with which to examine the action of the Notch pathway in a sp ecific cell fate decision in a vertebrate.