Study of Developmental and Molecular Processes Sorbs1 Regulated by using a combination of in vitro and in vivo models

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.
The goal of this project is to identify the developmental function of Sorbs1 and to characterize the underlying molecular events by exploiting a combination of in vivo (Zebrafish) and in vitro (Huvecs) models.
In vitro assays showed that Sorbs1 inactivation results in defects of migratory (not shown) and adhesive properties of endothelial cells which leads to problems in tubular formation and sprouting of this last ones, by controlling small Rho-GTPases activity.
Sorbs1 morphant zebrafish embryos, revealed abnormal development of venous angiogenic structures (such as caudal vein plexus (CVP) and subintestinal veins (SIV)), which could be related to the defects observed in vitro.
These results highlighted important developmental defects following Sorbs1 inactivation in two types of models, which led us to conclude that Sorbs1 could be an important regulator of cytoskeleton-dependent processes, especially during angiogenesis.