Rac function in epithelial tube morphogenesis.
Epithelial cell migration and morphogenesis require dynamic remodeling of the actin cytoskeleton and cell-cell adhesion complexes. Numerous studies in cell culture and in model organisms have demonstrated the small GTPase Rac to be a critical regulator of these processes; however, little is known about Rac function in the morphogenic movements that drive epithelial tube formation. Here, we use the embryonic salivary glands of Drosophila to understand the role of Rac in epithelial tube morphogenesis. We show that inhibition of Rac function, either through loss of function mutations or dominant-negative mutations, disrupts salivary gland invagination and posterior migration. In contrast, constitutive activation of Rac induces motile behavior and subsequent cell death. We further show that Rac regulation of salivary gland morphogenesis occurs through modulation of cell-cell adhesion mediated by the E-cadherin/beta-catenin complex and that shibire, the Drosophila homolog of dynamin, functions downstream of Rac in regulating beta-catenin localization during gland morphogenesis. Our results demonstrate that regulation of cadherin-based adherens junctions by Rac is critical for salivary gland morphogenesis and that this regulation occurs through dynamin-mediated endocytosis.
Pirraglia
Carolyn
C
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Jattani
Rakhi
R
Myat
Monn Monn
MM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D016923:Cell Death; D002465:Cell Movement; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006579:Heterozygote; D009154:Mutation; D011994:Recombinant Proteins / Q000737:chemistry; D012469:Salivary Glands / Q000196:embryology* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D015820:Cadherins; D029721:Drosophila Proteins; C090146:Rac1 protein, Drosophila; D011994:Recombinant Proteins; D051176:beta Catenin; D020744:rac GTP-Binding Proteins; D034281:Dynamins