Systematic in vivo analysis of Wnt secretory routes

点击翻译按钮获取中文摘要

The family of the Wnt glycoproteins, the ligands of the Wnt signaling pathway, are growth factors that are implicated in diverse processes during embryonic patterning in metazoans. The Wnt signaling pathway also plays key roles in various diseases, including cancer. We have conducted a genome-wide siRNA screen in human cells to identify novel regulators which are required for Wnt signaling. We made use of a synthetic siRNA library for the systematic knockdown of about 21,500 genes combined with epistatic cell-based assays for Wnt signaling activity. Comparisons between epistasis screens allowed us to identify a limited number of genes that act in different parts of the Wnt signaling cascade. We propose here to characterize a small number of relevant candidates and characterize them by in vivo by gain- and loss- of function analysis in both Drosophila as well as Xenopus. Relevant candidates will then be epistatically and biochemically analyzed in detail to unravel their mechanism of action. A particular focus will be on genes involved in Wnt secretion (Boutros) and mechanisms of receptor activation (Niehrs).