Rac1 GTPase acts downstream of ?PS1?PS integrin to control collective migration and lumen size in the Drosophila salivary gland.

ABSTRACT: During collective migration of the Drosophila embryonic salivary gland, the distal gland cells mediate integrin-based contacts with surrounding tissues while proximal gland cells change shape and rearrange. Here, we show that ?PS1?PS integrin controls salivary gland migration through Rac1 GTPase which downregulates E-cadherin in proximal and distal gland cells, and promotes extension of actin-rich basal membrane protrusions in the distal cells. In embryos mutant for multiple edematous wings (mew), which encodes the ?PS1 subunit of the ?PS1?PS integrin heterodimer, or rac1 and rac2 GTPases, salivary gland cells failed to migrate, to downregulate E-cadherin and to extend basal membrane protrusions. Selective inhibition of Rac1 in just the proximal or distal gland cells demonstrate that proximal gland cells play an active role in the collective migration of the whole gland and that continued migration of the distal cells depends on the proximal cells. Loss of rac1rac2 also affected gland lumen length and width whereas, loss of mew affected lumen length only. Activation of rac1 in mew mutant embryos significantly rescued the gland migration, lumen length and basal membrane protrusion defects and partially rescued the E-cadherin defects. Independent of mew, Rac regulates cell shape change and rearrangement in the proximal gland, which is important for migration and lumen width. Our studies shed novel insight into a Rac1-mediated link between integrin and cadherin adhesion proteins in vivo, control of lumen length and width and how activities of proximal and distal gland cells are coordinated to result in the collective migration of the entire salivary gland.

SUBMITTER: Pirraglia C 

PROVIDER: S-EPMC3878610 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature