Syndactyly of Ftl plus mice correlates with an imbalance in Bmp4 and Fgf8 expression

The most obvious phenotype of Ftl+ mice is a syndactyly of fore limbs chara cterised by a fusion of the tips of digits I to 4. The tempospatial express ion of genes involved in limb development revealed that patterning of Ftllimb buds is not affected by the mutation. However, an upregulation of Bmp4 in the anterior-distal region of the limb bud at d12.0 of embryonic develo pment is accompanied by a loss of Fgf8 expression in the distal part of the AER. Downstream target genes of Bmp action such as Msx1 and 2 are upregula ted. This induction of the signalling cascade indicates ectopic expression of functional Bmp4. Nevertheless, analysis of physical parameters of bones from adult mice revealed a reduction of the bone mass of the autopod. The d ata suggest a negative effect of Bmp4 on Fgf8 expression and a positive inf luence on the induction of bone elements. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.