During zebrafish angiogenesis, vessels sprout from the dorsal aorta and migrate dorsally between the somites before joining laterally to form the dorsal longitudinal anastomotic vessel (DLAV). However, the mechanisms underlying DLAV anastomosis and lumenisation are unclear. Now, Holger Gerhardt and colleagues study extracellular matrix protein, Svep1, in DLAV formation. Using live imaging of svep1 loss-of-function mutants and svep1 knockdown embryos (morphants), the authors observe gaps in the DLAV resulting from transient connections that regress, indicating that Svep1 stabilises vascular connections. However, this phenotype only presents in embryos that are anesthetised with tricaine, a treatment that also reduces blood flow. Indeed, they show that reduced blood flow and/or pressure (induced by cardiac troponin knockdown) cause DLAV defects in svep1 morphants, but shear-stress responses are unaffected. Using fluorescent reporter lines, the researchers show that svep1 expression is flow dependent and Svep1 deficiency increases the number of apln-expressing tip cells. Finally, activation of vascular endothelial growth factor (Vegf) signalling by knocking down flt1 (a Vegf decoy receptor) rescues DLAV connectivity, whereas Vegf inhibition aggravates DLAV defects. Together, these data show that Vegf signalling synergises with Svep1 in reduced flow conditions to perturb DLAV lumenisation and stability.
Svep1 connects anastomosis and blood flow
Svep1 connects anastomosis and blood flow. Development 15 March 2022; 149 (6): e149_e0605. doi:
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