Effects of alterations in Shh morphogen activity in the floor plate and the limb bud

(a) Sonic hedgehog gene Shh exons Limb—bud enhancer (b) Pedigrees in which Shh mutations segregate I C I I Carrier 1 2 II I O I D C II 1 2 3 4 5 6 7 8 IIIIOD.‘ IIDOII III Ill.1-2 I 3 4 .5 6 ‘ 7 m Mild Strong phenotype phenotype (deceased) ------------------- . --------------------------------- ; ---------------- \ Gain-of-function mutant alleles In limb-bud Loss-of—function mutant alleles in Shh exons are enhancer prolong Shh expression and are haploinsufficient and inherited in a dominant manner. inherited in a dominant manner. (c) Phenotypes associated with alterations in Shh activity it???” V t w HQ“ w-g’a Floor plate Limb buds I Loss of Shh activity in floor plate Shh expression in developing ‘ Prolonged Shh activity in limb bud causes cyclopia. 1 mouse embryo causes extra digit development. J