2 DISTINCT ROLES FOR RAS IN A DEVELOPMENTALLY-REGULATED CELL-MIGRATION

Receptor tyrosine kinases have been shown to promote cell movement in a variety of systems, The Ras protein, a well-documented downstream ef fector for receptor tyrosine kinases, may contribute to receptor tyros ine kinase-mediated motility, In the present study, we have examined t he role of Ras in the migration of a small subset of follicle cells, k nown as the border cells, during Drosophila oogenesis, A dominant-nega tive Ras protein inhibited cell migration when expressed specifically in border cells during the period when these cells normally migrate. W hen expressed prior to migration, dominant-negative Ras promoted prema ture initiation of migration, Conversely, expression of constitutively active Ras prior to migration resulted in a significant delay in the initiation step. Furthermore, the defect in initiation of border cell migration found in slbo(1), a mutation at the locus that encodes Droso phila C/EBP, was largely rescued by reducing Ras activity in border ce lls prior to migration, Taken together, these observations indicate th at Ras activity plays two distinct roles in the border cells: (1) redu ction in Ras activity promotes the initiation of that migration proces s and (2) Ras activity is required during border cell migration, We fu rther examined the possible involvement of two downstream effecters of Ras in border cell migration, Raf activity was dispensable to border cell migration while reduced Ral activity inhibited initiation, We the refore suggest that Ras plays a critical role in the dynamic regulatio n of border cell migration via a Raf-independent pathway.