PAX-3 IS NECESSARY BUT NOT SUFFICIENT FOR LBX1 EXPRESSION IN MYOGENICPRECURSOR CELLS OF THE LIMB

In vertebrates all skeletal muscles of trunk and limbs are derived fro m condensations of the paraxial mesoderm, the somites. Limb muscle pre cursor cells migrate during embryogenesis from somites to limb buds wh ere migration stops and differentiation occurs. We have characterized Ibx1 homeobox genes in chicken and mice and found them to be expressed in migrating limb muscle precursor cells in both species. Analysis of splotch mutant mice showed that Ibx1 and c-met are differently affect ed by the lack of Pax-3. Limb buds of splotch (Pax 3 mutant) mice were devoid of Ibx1 transcripts, while expression of c-met was still detec table at a low level. The presence of c-met-positive cells in splotch mice entering the limbs indicates that migration of cells from somites to limbs is not entirely dependent on Pax-3. We show that induction o f epithelial to mesenchymal transition of Pax-3-positive cells by SF/H GF was not sufficient to induce ectopic lbx-1 expression at the inter- limb level, while ectopic limb formation was able to activate Ibx1 exp ression. We postulate that Pax-3 is necessary for Ibx1 expression in t he lateral tips of somites but additional, yet unknown signals derived from limb buds are needed to initiate Ibxl expression. The role of li mb bud-derived signals involved in targeted muscle precursor cell migr ation, and Ibxl activation was further confirmed by analysis of explan ted somite/limb bud co-cultures in collagen gels. (C) 1995 Elsevier Sc ience Ireland Ltd. All rights reserved.