Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm

Mesodermal progenitors arise in the Drosophila embryo from discrete cluster s of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-fu nction and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of uniqu e combinations of intercellular signals. Initially, the intersection betwee n the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two rec eptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor recep tor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By mon itoring the expression of the diphosphorylated form of mitogen-associated p rotein kinase (MAPK), we found that these RTKs are activated in small clust ers of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localiz ed RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreove r, DER and Htl are differentially involved in the specification of particul ar progenitors. We conclude that distinct cellular identity codes are gener ated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in th e progressive determination of embryonic mesodermal cells.