Formin 1 (FMN1)

Mutation at the mouse """limb deformity""" (ld) locus disrupts embryonic pattern formation, resulting in a reduction and fusion of the distal bones and digits of all limbs as well as variable incidence of renal aplasia. the large and complex LD gene has the capacity to generate a number of alternatively spliced mRNA transcripts encoding nuclear protein isoforms called formins. Mesenchymal gremlin expression is lost in limb buds of mouse embryos homozygous for the ld mutation, which disrupts establishment of the Shh/Fgf4 feedback loop. Grafting gremlin-expressing cells into ld mutant limb buds rescued Fgf4 expression and restored the Shh/Fgf4 feedback loop.Analysis of Shh-null mutant embryos revealed that Shh signaling is required for maintenance of gremlin and Fmn1, the gene disrupted by the ld mutations.