Rac1 GTPase acts downstream of αPS1βPS integrin to control collective migration and lumen size in the Drosophila salivary gland

• Published in: Developmental biology 2013-05, Vol.377 (1), p.21-32
• Main Authors: Pirraglia, Carolyn, Walters, Jenna, Ahn, Nancy, Myat, Monn Monn
• Format: Article
• Language: English
• Subjects: Adhesion; Animals; Cadherin; cadherins; Cadherins - metabolism; Cell Movement; Cell Shape; Cell Surface Extensions - metabolism; Collective migration; Down-Regulation; Drosophila; Drosophila melanogaster - anatomy & histology; Drosophila melanogaster - cytology; Drosophila melanogaster - embryology; Drosophila melanogaster - enzymology; Drosophila Proteins - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; guanosinetriphosphatase; Integrin; Integrin alpha Chains - metabolism; integrins; Integrins - metabolism; Lumen; Models, Biological; mutants; Mutation - genetics; Organ Size; rac GTP-Binding Proteins - metabolism; Rac GTPase; rho GTP-Binding Proteins - metabolism; salivary glands; Salivary Glands - anatomy & histology; Salivary Glands - cytology; Salivary Glands - enzymology; tissues; Tube; wings
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2013.02.020

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 αPS1βPS 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 αPS1 subunit of the αPS1βPS 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. ► Integrins control Drosophila embryonic salivary gland migration through Rac GTPases.► Rac GTPases downregulate E-cadherin and promote membrane protrusion.► Rac1 function is required for migration of proximal and distal salivary gland cells.► Proximal salivary gland cells undergo morphogenic movements independent of distal cells.► Integrins and Rac control salivary gland lumen size.