EVIDENCE FOR GENETIC-CONTROL OF SONIC HEDGEHOG BY GLI3 IN MOUSE LIMB DEVELOPMENT

Sonic hedgehog (Shh) expression in the developing limb is associated w ith the zone of polarising activity (ZPA), and both are restricted to the posterior part of the limb bud. We show that the expression patter ns of Shh and Gli3, a member of the Gli-family believed to function in transcriptional control, appear to be mutually exclusive in limb buds of mouse embryos. In the polydactyly mouse mutant extra toes (Xt), po ssessing a null mutation of Gli3, Shh is additionally expressed in the anterior region of the limb bud. The transcript of Ptc, the putative receptor for Shh protein, can be detected anteriorly as well. Other ge nes known to be involved in limb outgrowth and patterning, like Fibrob last growth factor (Fgf), Bone morphogenetic protein (Bmp), and Herd a re misexpressed in relation to the ectopic Shh expression domain in Xt limb buds. This data suggest that Gli3 is a regulator of Shh expressi on in mouse limb development. (C) 1997 Elsevier Science Ireland Ltd.