csal1 is controlled by a combination of FGF and Wnt signals in developing limb buds

While some of the signaling molecules that govern establishment of the limb axis have been characterized, little is known about the downstream effecto r genes that interpret these signals. In Drosophila, the spalt gene is invo lved in cell fate determination and pattern formation in different tissues. We have cloned a chick homologue of Drosophila spalt, which we have termed csal1, and this study focuses on the regulation of csal1 expression in the limb bud. csal1 is expressed in limb buds from HH 17 to 26, in both the ap ical ectodermal ridge and the distal mesenchyme. Signals from the apical ri dge are essential for csal1 expression, while the dorsal ectoderm is requir ed for csal1 expression at a distance from the ridge. Our data indicate tha t both FGF and Wnt signals are required for the regulation of csal1 express ion in the limb. Mutations in the human homologue of csal1, termed Hsal1/SA LL1, result in a condition known as Townes-Brocks syndrome (TBS), which is characterized by preaxial polydactyly. The developmental expression of csal 1 together with the digit phenotype in TBS patients suggests that csal1 may play a role in some aspects of distal patterning. (C) 2000 Academic Press.