The proposed study is part of the applicant's broad interest in the genetic mechanisms that establish distinct tissues and organs during embryogenesis, including both the initial instructions that define an organ and the subsequent cell-cell signaling, changes in gene expression, and cellular movements that build the differentiated organ and maintain its identity. The applicant's study of salivary gland development in Drosophila embryos has led to a model for the initial determination of cells in the salivary duct primordia. Salivary gene expression is activated by the homeotic gene Sex combs reduced, and the salivary gland and salivary duct primordia are distinguished from each other by the opposing activities of the EGF receptor signaling pathway and the transcription factor fork head. Shortly after their determination, both the pregland and preduct cells invaginate and within 3 hours become functional salivary glands and ducts. This proposal focuses on the genetic control of the invaginations in these two tissues. Multiple regulatory genes appear to interact to produce the distinctly different pregland and preduct invaginations. The applicant plans to examine the roles of three genes or gene pairs, fork head, Notch/Delta, and X31, that are involved in invagination of the pregland cells and one gene, eyegone, that is required for invagination of the preduct cells. Because the functions of neither X31 nor eyegone have been previously determined, and because both genes appear to be important, not only for salivary development but also for other determinative or morphogenetic events in the embryo, their involvement in other early embryonic invaginations or in specification of the optic primordia will also be studied. The salivary and nonsalivary studies are expected to reinforce each other and lead to a more rapid and deeper understanding of the function of these genes. There are four specific aims for these experiments: (i) to establish the role of fork head in salivary gland invagination; (ii) to determine whether Notch-Delta signaling is important for salivary gland invagination; (iii) to isolate X31 mutations and use them to establish whether this newly identified gene is required for a series of embryonic invaginations; and (iv) to establish the role of the eyegone gene in both salivary duct and eye development.
| Harris, Katherine E; Schnittke, Nikolai; Beckendorf, Steven K (2007) Two ligands signal through the Drosophila PDGF/VEGF receptor to ensure proper salivary gland positioning. Mech Dev 124:441-8 |
| Kolesnikov, Tereza; Beckendorf, Steven K (2007) 18 wheeler regulates apical constriction of salivary gland cells via the Rho-GTPase-signaling pathway. Dev Biol 307:53-61 |
| Harris, Katherine E; Beckendorf, Steven K (2007) Different Wnt signals act through the Frizzled and RYK receptors during Drosophila salivary gland migration. Development 134:2017-25 |
| Kolesnikov, Tereza; Beckendorf, Steven K (2005) NETRIN and SLIT guide salivary gland migration. Dev Biol 284:102-11 |
| Chandrasekaran, Vidya; Beckendorf, Steven K (2005) Tec29 controls actin remodeling and endoreplication during invagination of the Drosophila embryonic salivary glands. Development 132:3515-24 |
