CONTROL OF CELL PATTERN IN THE NEURAL-TUBE BY THE ZINC-FINGER TRANSCRIPTION FACTOR AND ONCOGENE GLI-1

Sonic hedgehog (Shh) is a putative morphogen secreted by the floor pla te and notochord, which specifies the fate of multiple cell types in t he ventral aspect of the vertebrate nervous system. Since in Drosophil a the actions of Hh have been shown to be transduced by Cubitus interr uptus (Ci), a zinc finger transcription factor, we examined whether a vertebrate homolog of this protein can mediate the functions of Shh in the vertebrate nervous system. Here, we demonstrate that expression o f Gli-1, one of three vertebrate homologs of Ci, can be induced by Shh in the neural tube. Further, ectopic expression of Gli-1 in the dorsa l midbrain and hindbrain of transgenic mice mimics the effects of ecto pically expressed Shh-N, leading to the activation of ventral neural t ube markers such as Ptc, HNF-3 beta, and Shh; to the suppression of do rsal markers such as Pax-3 and AL-1; and to the formation of ectopic d orsal clusters of dopaminergic and serotonergic neurons. These finding s demonstrate that GLI-1 can reproduce the cell patterning actions of Shh in the developing nervous system and provide support for the hypot hesis that it is a mediator of the Shh signal in vertebrates.