GLI2 IS REQUIRED FOR INDUCTION OF FLOOR PLATE AND ADJACENT CELLS, BUTNOT MOST VENTRAL NEURONS IN THE MOUSE CENTRAL-NERVOUS-SYSTEM

Induction of the floor plate at the ventral midline of the neural tube is one of the earliest events in the establishment of dorsoventral (d /v) polarity in the vertebrate central nervous system (CNS), The secre ted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream comp onents of this signalling pathway have been identified, including memb ers of the Gli transcription factor family. In this study, we have exa mined d/v patterning of the CNS in Gli2 mouse mutants. We have found t hat the floor plate throughout the midbrain, hindbrain and spinal cord does not form in Gli2 homozygotes. Despite this, motoneurons and vent ral interneurons form in their normal d/v positions at 9.5 to 12.5 day s postcoitum (dpc), However, cells that are generated in the region fl anking the floor plate, including dopaminergic and serotonergic neuron s, were greatly reduced in number or absent in Gli2 homozygous embryos . These results suggest that early signals derived from the notochord can be sufficient for establishing the basic d/v domains of cell diffe rentiation in the ventral spinal cord and hindbrain, Interestingly, th e notochord in Gli2 mutants does not regress ventrally after 10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-fing er-deletion double homozygous mutants appeared similar to Gli2 homozyg otes, indicating that neither gene is required downstream of Shh for t he early development of ventral cell fates outside the ventral midline .