The long-term goal of the proposed research is to understand how signals emanating from cell-cell contacts specify cellular polarity and cell fate. This work will focus on how signaling via the tyrosine kinase SRC-1 interfaces with a Wnt signaling pathway to control endoderm specification and division orientation in early C. elegans embryos. An integrated set of proteomic, bio-informatic, and genetic studies will be employed to identify components of the SRC-1 pathway.
The aims will include, i) the identification of SRC-1 interacting proteins, and ii) a bioinformatic analysis to identify candidate SRC-1 pathway genes. These two aims will be coupled to powerful in vivo genetic assays using RNAi that will facilitate the identification of physiologically relevant genes among the many candidates identified. Finally, a third aim will utilize an open-ended screen for temperature-sensitive mutants that will identify new genes involved in SRC-1 signaling. These studies will shed light on how SRC-1 and WNT signaling converge to regulate a common set of downstream factors, and will provide a paradigm for understanding how these key signaling pathways, important in both development and cancer, interact to control development in a powerful genetic model system.
| Liu, Ji; Maduzia, Lisa L; Shirayama, Masaki et al. (2010) NMY-2 maintains cellular asymmetry and cell boundaries, and promotes a SRC-dependent asymmetric cell division. Dev Biol 339:366-73 |
