Essential roles of Gli3 and sonic hedgehog in pattern formation and developmental anomalies caused by their dysfunction.

Pattern formation along the body axis directs the proportion of different types of cells required for functional tissue structures. The secreted protein sonic hedgehog (Shh) and zinc finger transcription factor Gli3 are key players in pattern formation during brain and limb development; the antagonistic action of Shh towards Gli3 may be crucial for pattern formation. Recent findings from Shh/Gli3 double homozygous mutants suggest that a balance of both activities is required for the production of the normal proportion of different cell types during organogenesis. This conclusion contrasts with the alternative hypothesis that a Shh gradient directs the specification of several different cell types. The observations reviewed here offer a new perspective on understanding the pathogenesis of human birth defects caused by mutations of the Shh and Gli3 genes.