Sim1 and Sim2 expression during chick and mouse limb development.

The Drosophila Single minded (Sim) transcription factor is a master regulator of cell fate during midline development. The homolog mouse Sim1 and Sim2 genes are important for central nervous system development. Loss of mSim1 activity leads to an absence of specific neuroendocrine lineages within the hypothalamus, while overexpression of mSim2 leads to behavioural defects. We now provide evidence that vertebrate Sim genes might be important for limb muscle formation. We have examined by in situ hybridisation the expression of the Sim1 and Sim2 genes during limb development in chick and mouse embryos. The expression of both Sim genes is mainly associated with limb muscle formation. We found that each Sim gene has a similar temporal and spatial expression pattern in chick and mouse embryonic limbs, although with some differences for the Sim2 gene between species. In chick or mouse embryonic limbs, Sim1 and Sim2 display non-overlapping expression domains, suggesting an involvement for Sim1 and Sim2 proteins at different steps of limb muscle formation. Sim1 gene expression is associated with the early step of muscle progenitor cell migration in chick and mouse, while the Sim2 gene is expressed just after the migration process. In addition, chick and mouse Sim2 gene expression is enhanced in limb ventral muscle masses versus dorsal ventral muscle masses. Our results provide a basis for further functional analysis of the Sim genes in limb muscle formation.