Abstract :
[en] A large number of studies have shown that the Sorbs1 adaptor protein, as well as the other members of the SoHo family, are involved in the regulation of cytoskeletal dynamics. Consequently, these members participate in numerous cytoskeleton-dependent cellular processes, such as cellular migration and adhesion. However, the biological processes in which SoHo proteins perform their cytoskeleton regulatory functions remain unknown.
The aim of this study was to uncover the potential role of Sorbs1 in vascular development, a biological process that is highly dependent on endothelial cell cytoskeleton morphogenesis.
To this end, we used CRISPR/Cas9- and morpholino-based inactivation of Sorbs1 in the zebrafish model.
Both approaches demonstrate that Sorbs1 is required for secondary sprouting and subsequent formation of venous angiogenic and lymphangiogenic structures that specifically derive from the cardinal vein. However, Sorbs1 depletion does not affect arterial angiogenesis development.
Mechanistically, we show that Sorbs1 controls endothelial cell properties such as migration and adhesion by regulating the activity of RhoA, a member of the RhoGTPase family.
Surprisingly, the knock-down of another member of the SoHo family, Sorbs2, has no significant impact on venous or lymphatic angiogenesis. In contrast to Sorbs1, Sorbs2 is specifically required for endothelial cell migration from the dorsal aorta and for proper intersegmental vessel development.
Altogether, we were able to identify for the first time a developmental function of Sorbs1 in venous and lymphatic angiogenesis.
