stumps, a Drosophila gene required for fibroblast growth factor (FGF)-directed migrations of tracheal and mesodermal cells

Fibroblast growth factors (FGFs) bind to FGF receptors, transmembrane tyros ine kinases that activate mitogenic, motogenic, and differentiative respons es in different tissues. While there has been substantial progress in eluci dating the Ras-MAP kinase pathway that mediates the differentiative respons es, the signal transduction pathways that lead to directed cell migrations are not well defined. Here we describe a Drosophila gene called stumps that is required for FGF-dependent migrations of tracheal and mesodermal cells. These migrations are controlled by different FGF ligands and receptors, an d they occur by different cellular mechanisms: the tracheal migrations occu r as part of an epithelium whereas the mesodermal migrations are fibroblast -like. In the stumps mutant, tracheal cells fail to move out from the epith elial sacs, and only rudimentary tracheal branches form. Mesodermal cells f ail in their dorsal migrations after gastrulation. The stumps mutation does not block all FGF signaling effects in these tissues: both random cell mig rations and Ras-MAP kinase-mediated induction of FGF-specific effector gene s occurred upon ectopic expression of the ligand or upon expression of a co nstitutively activated Ras protein in the migrating cells. The results sugg est that stumps function promotes FGF-directed cell migrations, either by p otentiating the FGF signaling process or by coupling the signal to the cell ular machinery required for directed cell movement.