Study of Developmental and Molecular Processes Regulated by Sorbs1 using a Combination of in vitro and in vivo models Alexandra Veloso1, Anouk Bleuart1, Maud Martin1, Jonathan Bruyr1, Marie-Ange Mavaccarella1, and Franck Dequiedt1

SoHo proteins belong to a family that includes three members: Sorbs1 (Cbl associated protein CAP/ponsin), Sorbs2 (Arg-Binding Protein 2, ArgBP2) and Sorbs3 (Vinexin). These proteins share a similar structure with a SoHo domain in N-terminal region and three SH3 domains in carboxy terminal region. These characteristic domains bind to several signaling molecules involved in a variety of cytoskeleton-related processes, and SoHo family members are thus thought to function as adaptor proteins. However, the precise role of these proteins in the cytoskeleton regulation and associated biological functions remains unknown. It is well established that cytoskeleton regulation is critical for various developmental events including angiogenesis, the process by which new blood vessels develop from pre-existing ones, and myogenesis, the process responsible for muscle formation and regeneration. The goal of this project is to identify the developmental function of Sorbs1 and characterize the underlying molecular events by exploiting a combination of in vivo (Zebrafish) and in vitro models. Phenotype analysis revealed that Morpholino-mediated knock-down of Sorbs1 induces abnormal development of cardiac, angiogenic and muscles structures. Knock-down zebrafish embryos were unable to form cardiac looping and present a cardiac edema. Also, it was noticed that tail morphology was altered by Sorbs1 knock-down suggesting that Sorbs1 plays a role in trunk muscle formation. Finally, the development of venous angiogenic structures, such as caudal vein plexus (CVP) and subintestinal veins (SIV), was specifically affected by Sorbs1inactivation. Interestingly, Sorbs1 seems to have a specific role in venous angiogenesis (CVP and SIV), since arterial angiogenic structures, such as Intersegmental vessels, were not affected in Sorbs1 morphants. In conclusion, these preliminary results of our work highlighted important developmental defects by consequence of Sorbs1 inactivation in Zebrafish. Some of these defects appear to be regulated by angiogenesis and myogenesis, two developmental processes for which the therapeutic implications are undeniable.