Impairment of Sox9 Expression in Limb Buds of Rats Homozygous for Hypodactyly Mutation

Rat hypodactyly (hd) is an autosomal re- cessive mutation manifesting in homozygotes as re- duction or loss of digits II and III. We mapped the hd allele to a short segment of chromosome 10, contain- ing 16 genes. None of these genes has been shown to influence limb development yet. In situ hybridization showed no changes in several important patterning genes (Shh, Fgf8, Bmp2, 4, 7). However, we found that expression of cartilage condensation marker Sox9, and Bmp receptor Bmpr1b (acting as an up- stream activator of Sox9 expression) is absent from the subepithelial mesenchyme of the digit condensa- tions II and III. The failure of the chondrogenic con- densations to extend towards the subepithelial mes- enchyme may reduce the size of digit primordia and underlie the subsequent loss of phalanges and reduc- tion of metacarpals/metatarsals in hd rats.