SPONGE SIGNALING · Using sponges as a model to examine the evolution of the Wnt/beta-catenin signaling pathway

The central concept of the field of evolutionary developmental biology (evo-devo) is that changes in development give rise to changes in form. While recent advances in both comparative genomics and experimental biology have greatly accelerated the rate of discovery in evo-devo by facilitating the study of non-traditional experimental models, we have only begun to understand how developmental mechanisms themselves first evolved, and how these ancient evolutionary events shaped the morphological evolution of lineages that persists today. The focus of this proposal is on the evolution of the Wnt/beta-catenin developmental signaling pathway and its role in modern sponges, one of the earliest branching metazoan lineages. In bilaterians, the Wnt/beta-catenin pathway plays a critical role during animal development, as it controls cell differentiation, proliferation and apoptosis by regulating the expression of a high number of target genes. In addition to its normal functions, misregulation of this pathway can lead to serious diseases in humans, such as cancer. The discovery of conserved homologs of the Wnt/beta-catenin pathway in sponges raises questions about whether a functional Wnt/beta-catenin pathway is present in sponges and what its role may be in organisms of such simplicity – they lack many features of bilaterians, such as muscles, nerves and a gut. The specific aims of this study are to (1) test whether the sponge homologs of Wnt/beta-catenin components interact (2) identify the tissue-specific and subcellular localization patterns of beta-catenin and TCF (these proteins form the transcriptional complex downstream of the Wnt/beta-catenin pathway) (3) identify which target genes are regulated by the beta-catenin/TCF transcriptional complex and (4) develop techniques for studying gene function in vivo in sponges. The overall goal of the proposed research is to learn more about how metazoan morphology evolves, and about how signaling pathways themselves evolve.