An instructive function for Notch in promoting gliogenesis in the zebrafish retina

The GaI4-UAS technique has been used to misexpress a constitutively active Notch receptor variant (notch1a-intra) in the developing zebrafish retina. This is the first study to use this technique to misexpress genes and asses s their function in neural development of the zebrafish. Expression of acti vated Notch1a either ubiquitously, driven by a heat-shock70 promoter, or in a spatially regulated manner, controlled by the deltaD promoter, causes a block in neuronal differentiation that affects all cell types, Developing c ells take on either a glial fate or remain undifferentiated, A large number of cells eventually undergo apoptosis. These phenotypic effects of activat ed Notch1a are expressed cell autonomously. Cells within central regions of the retina adopt a glial fate if they express activated Notch1a in a time window that extends from 27 to 48 hours postfertilization. This period corr esponds mainly to the time of origin of ganglion cells in the normal retina . Activation of notch1a at later stages results in defects in cell type spe cification that remain restricted to the ciliary marginal zone, whereas neu ronal types are specified normally within the central region. These observa tions indicate that glial differentiation is initiated by Notch1a-intra exp ressing cells, which become postmitotic in the same time window. Our result s strongly suggest that Notch1a instructs a certain cell population to ente r gliogenesis, and keeps the remaining cells in an undifferentiated state. Some or all of these cells will eventually succumb to apoptosis.