Functional Genomic Approaches Targeting the Wnt Signaling Network

The sequencing of whole genomes, including those of model organisms, has provided an unprecedented resource to the research community to make sense of the genetic code. However, it is the advent of novel functional genomic technologies that have been truly instrumental in bridging the gap between gene sequence and gene function. The past few years have witnessed a rapid growth in the development and implementation of high-throughput screening (HTS) technologies that researchers are now using to discover gene-function in an unbiased, systematic, time and cost-efficient manner. One of the most promising functional genomic approach that has emerged in the past few years is based on RNA-interference (RNAi) in which the introduction of double-stranded RNA (dsRNA) or short-interfering RNA (siRNA) into cells or whole organisms can effectively suppress endogenous gene expression. The RNAi-based screening technology has made it feasible to query the function of whole genomes in the regulation of conserved cell-signaling pathways and the crosstalk between them in signaling networks that are known to influence important cell biological functions, such as cell proliferation and growth, cell morphology, cell adhesion and cell death. In this review we discuss the application, advantages and limitations of RNAi and other post-genomic technologies in the identification of novel modulators of cell-signaling pathways, with a focus on the Wnt signaling pathway. We also discuss the future scope and utility of designing additional variants of these genome-scale screens.