DIMINISHED SONIC HEDGEHOG SIGNALING AND LACK OF FLOOR PLATE DIFFERENTIATION IN GLI2 MUTANT MICE

Floor plate cells at the midline of the neural tube are specified by h igh-level activity of Sonic hedgehog (Shh) secreted by notochord, wher eas motor neurons are thought to be specified by a lower level activit y of Shh secreted in turn by floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus functions as a transcription factor activating Hedgehog-responsive genes. We report that the expres sion of known Shh-responsive genes such as Ptc and Gli1 is downregulat ed in mutant mice lacking Gli2 function. Gli2 mutants fail to develop a floor plate yet still develop motor neurons, which occupy the ventra l midline of the neural tube. Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction.