The Notch (N) signaling pathway defines an evolutionarily conserved cell interaction mechanism that controls a number of cell fate choices in distinct developing tissues. Mutations in Notch signaling pathway elements are associated with human pathology demonstrating the important role Notch signaling performs during development. Mutations in mastermind (mam) exhibit neurogenic phenotypes and display extensive genetic interactions with Notch pathway components suggesting that Mastermind plays an important role in the Notch signaling pathway. Despite the similarity to nuclear regulatory proteins the function of Mam remains unknown, as well as its role in Notch signaling. Using Drosophila melanogaster as a model system, the goal of this proposal is to examine the physiological role of mam and hopefully to elucidate, at the genetic and molecular level, the mechanism by which mam functions within the Notch signaling pathway. The following specific aims are proposed: 1. Identify extragenic factors affecting mastermind function: A genetic screen will be carried out aimed at isolating dominant modifiers of mastermind function in the developing wing. 2. Identify and analyze mastermind molecular interactors: A molecular analysis will complement Specific Aim 1 in identifying intracellular effectors of Mastermind.
|Hurlbut, Gregory D; Kankel, Mark W; Artavanis-Tsakonas, Spyros (2009) Nodal points and complexity of Notch-Ras signal integration. Proc Natl Acad Sci U S A 106:2218-23|