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Biologie du Développement de Villefranche-sur-Mer

Evolution of Wnt signaling functions

Evolution of Wnt signaling functions during deuterostome development: Wnt ligands and Frizzled receptors
The Wnt proteins constitute a large family of cysteine-rich secreted glycoproteins that have been identified in most metazoan animals. Intercellular Wnt signals are triggered by the association of secreted Wnt proteins and their cognate receptors, Frizzled (Fz), which are members of the G protein-coupled receptor family. To date, three main Wnt cascades have been reported (Fig. 1): the well-characterized canonical Wnt pathway mediated by the intracellular stabilization of β-catenin, and two less-characterized non-canonical Wnt pathways, the planar cell polarity (PCP) and the Wnt/Ca2+ pathways. Together, they are involved in the control of various biological processes in metazoan embryos and adults ranging from cell fate establishment and morphogenesis to stem cell renewal.
In the EvoInSiDe team, we aim at determining, in our three animal models, sea urchins, amphioxus and lampreys (Fig. 2), the developmental functions of Wnt ligands and Fz receptors during embryogenesis. To this end, we employ classical embryological experiments based on gain and loss of function assays and microscopy-based analyses (including microinjection, pharmacological treatments, gene expression profiles and immunohistochemical studies). In addition, we plan to identify genes targeted by Wnt signaling through large-scale transcriptomic and genomic screens. In sea urchins, we have already characterized the function of two Fz receptors, Fz5/8 and Fz1/2/7, and of one Wnt ligand, Wnt6. We have shown that Fz5/8 regulates archenteron invagination at the onset of gastrulation through the control of the PCP pathway. Likewise, we have established that Fz1/2/7 activated by Wnt6 triggers the nuclear accumulation of β-catenin in a selective subset of vegetal blastomeres at the 32-cell stage, an event that is critical for subsequent endoderm specification.
We are currently investigating the involvement of the two other sea urchin Fz receptors as well as their Wnt ligands. In parallel, we are performing the same kind of experiments in amphioxus, and, to a lesser extent, in lampreys. Ultimately, the combination of the data from our model organisms will provide insights into the evolutionary diversification in deuterostomes of the Wnt signaling network in deuterostomes, including both canonical and non-canonical pathways.

 

 

Figure 1. Overview of the main Wnt signaling pathways, including the canonical (β-catenin) and two non-canonical (planar cell polarity and calcium) pathways (modified from Croce et al., 2006, Dev. Biol., 300:121-131).

 


Figure 2. Simplified phylogeny of metazoan animals (modified from Campo-Paysaa et al., 2008, Genesis, 46:640-656).

Michael Schubert - 25/09/17

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