Evolution of Wnt signaling in metazoans

   Wnt signaling is one of the most fundamental intercellular signaling systems of multicellular animals and is required for the regulation of numerous biological processes both during embryogenesis and in adults. Within a target cell, the intercellular Wnt signaling system can trigger several different intracellular signal transduction cascades, including three main ones: the canonical Wnt/b-catenin pathway and the non-canonical planar cell polarity and calcium pathways. As of today, most studies on Wnt signaling have focused on the roles of these three intracellular pathways and their cross talk during development. In contrast, virtually nothing is known about the mechanisms underlying the recognition and binding specificities of individual Wnt proteins to their cognate Frizzled (Fzd) receptors and about the molecular processes leading to the activation, by a given ligand-receptor couple, of a particular intracellular Wnt pathway. This lack of knowledge, in turn, also hampers the characterization of the global biological responses triggered by Wnt signaling, both on a genomic and developmental level.

   In the EvoInSiDe team, we are addressing this shortcoming using both genomic and embryological approaches in comparative analyses with different animal model systems. Our current investigations include the characterization of the Wnt and Fzd complements from a large variety of different metazoan animals in an effort to retrace the evolutionary history of the Wnt and Fzd families. This project makes use of bioinformatic approaches, such as phylogenetic analyses, genome-wide synteny screens as well as ancestral sequence reconstruction. In parallel, we are also studying the roles of Wnt signaling during development, chiefly in sea urchins and amphioxus. In sea urchins, we have, for example, already characterized the spatiotemporal expression patterns of all Wnt ligands and Fzd receptors from the European species Paracentrotus lividus. We have further established that a specific Wnt/Fzd couple (Wnt6 and Frizzled1/2/7) is required, in this species, for the activation of canonical Wnt/b-catenin signaling in a subset of vegetal blastomeres to establish endodermal cell fate and that another Fzd receptor (Frizzled5/8) controls the initiation of gut invagination, likely through the activation of the non-canonical planar cell polarity pathway.

   Our goal is now to identify the totality of Wnt/Fzd couples forming during sea urchin and amphioxus development and to characterize their functions, including both the genomic responses triggered and their developmental readouts in embryos and larvae. This project will thus reveal a trove of information on the most fundamental aspects of Wnt signaling: its activation, its target genes, and its biological roles during development. Comparisons of these results with available information from other animal models will ultimately allow the establishment of an evolutionary roadmap for the diversification of the Wnt signaling system in multicellular animals.