The PDZ domain protein Arc is required for proper invagination of the embryonic salivary glands. Rika Maruyama1,2, Sarah Hughes1, Deborah Andrew2. 1) Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada; 2) Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD.
Tubulogenesis is an important process during organogenesis since many organs, including the lungs, kidneys and vasculature, as well as many secretory organs, are composed of sophisticated tubular networks. Invagination is a key early step in the formation of tubes from polarized epithelial sheets; however, the molecular mechanisms coordinating invagination remain unclear. Fork head (Fkh), the founding member of the FoxA family of winged-helix transcription factors, is required for invagination of the salivary gland primordia to form salivary gland tubes. In a screen for Fkh targets that mediate salivary gland morphogenesis (1), we identified the arc gene. Arc is an adjerens junction-associated PDZ domain protein previously shown to be required for wing and eye development (2). arc mRNA is detected in multiple embryonic tubular organs, including the trachea, Malpighian tubules and the salivary glands, where arc expression depends on fkh. To examine the embryonic function of arc in more detail, we created arc null (KO) mutants by homologous recombination. arc maternal-zygotic KO mutants exhibit a range of morphological phenotypes linked to defects in invagination, including broader salivary gland invagination pits. Overexpression of arc in salivary glands using fkh-Gal4 blocked salivary gland invagination and caused mislocalization of the apical membrane protein Crumb (Crb). We are continuing to explore the link between Arc and Crb, and the mechanisms through which Arc contributes to salivary gland invagination.
1. Maruyama et. al., PLoS One. 2011; 6(6):e20901
2. Liu and Lengyel, Dev. Bio. 2000; May 15; 221(2): 419-34.