The Fused toes ( Ft) Mouse Mutation Causes Anteroposterior and Dorsoventral Polydactyly

Abstract

Mouse mutants have been proven to be a valuable system to analyze the molecular network governing vertebrate limb development. In the present study, we report on the molecular and morphological consequences of the Fused toes ( Ft) mutation on limb morphogenesis in homozygous embryos. We show that Ft affects all three axes as the mutant limbs display severe distal truncations of skeletal elements as well as an anteroposterior and an unusual form of dorsoventral polydactyly. Ectopic activation of the Shh signalling cascade in the distal-most mesoderm together with malformations of the AER likely account for these alterations. Moreover, we provide evidence that a deregulated control of programmed cell death triggered by Bmp-4 and Dkk-1 significantly contributes to the complex limb phenotype. In addition, our analysis reveals a specific requirement of the genes deleted by the Ft mutation in hindlimb morphogenesis.