The segregation of founder cells from the somatic mesoderm is a prerequisite for the formation of body wall muscles in theDrosophilaembryo. The myogenic basic helix-loop-helix protein, Nautilus (Nau), is expressed in a subset of these founder cells in medial and lateral positions in the somatic mesoderm. Mutations in thewingless(wg) gene, which encodes a secreted growth factor, lead to the complete loss of Nau-expressing medial muscle precursor cell clusters, but not lateral clusters. Using the GAL4/UAS system, we demonstrate that thewg-derived signal can originate from either ectoderm or mesoderm to influencenauexpression. By using a temperature-sensitivewgallele, we also show thatwgfunction is required during and after gastrulation for the formation of Nau-expressing medial muscle precursor cell clusters. Our results, combined with recent studies from chick, suggest a conserved role for Wg signaling pathways during muscle development.