GLI ZIC FACTORS PATTERN THE NEURAL PLATE BY DEFINING DOMAINS OF CELL-DIFFERENTIATION/

Three cell types differentiate in the early frog neural plate: neural crest at the lateral edges, floorplate at the midline and primary neur ons in three bilateral stripes. Floorplate cells and ventral neurons a re induced by Sonic hedgehog(1,2) (Shh) and neural crest and dorsal. n eurons are induced by epidermal factors such as bone morphogenetic pro teins (BMPs)(3). Neurogenesis in a subset of cells within the stripes involves lateral inhibition(4). However, the process by which pools of precursors are defined in stereotypic domains in response to inductiv e signals is unknown. Here we show that frog Zic2 encodes a zinc-finge r transcription factor of the Gli superfamily which is expressed in st ripes that alternate with those in which primary neurons differentiate and overlap the domains of floorplate and neural crest progenitors. Z ic2 inhibits neurogenesis and induces neural crest differentiation. Co nversely, Gli proteins are widely expressed, induce neurogenesis and i nhibit neural crest differentiation. Zic2 is therefore a vertebrate pr e-pattern gene, encoding anti-neurogenic and crest-inducing functions that counteract the neurogenic but not the floorplate-inducing activit y of Gli proteins. We propose that the combined function of Gli/Zic ge nes responds to inductive signals and induces patterned neural cell di fferentiation.