Akt is required for artery formation during embryonic vascular development

Abstract

One of the first events in the development of the cardiovascular system is morphogenesis of the main embryonic artery, the dorsal aorta (DA). The DA forms via a conserved genetic process mediated by the migration, specification, and organization of endothelial progenitor cells into a distinct arterial lineage and vessel type. Several angiogenic factors activate different signaling pathways to control DA formation, however the physiological relevance of distinct kinases in this complex process remains unclear. Here, we identify the role of Akt during early vascular development by generating mutant zebrafish lines that lack expression of akt isoforms. Live cell imaging coupled with single cell RNA sequencing of akt mutants reveal that Akt is required for proper development of the DA by sustaining arterial cell progenitor specification and segregation. Mechanistically, inhibition of active FOXO in akt mutants rescues impaired arterial development but not the expression of arterial markers, whereas Notch activation rescues arterial marker expression. Our work suggests that Akt activity is critical for early artery development, in part via FOXO and Notch-mediated regulation.

High glucose treatment induced nuclei aggregation of microvascular endothelial cells via foxo1a-klf2a pathway

“…Although the role of foxo1a and foxo1b in zebrafish vasculature has been little studied, a recent study has reported that foxo1 is involved in embryonic vascular development [57]. Investigations have revealed that the depletion of foxo1, specifically in endothelial cells, enhances metabolic activity and promotes angiogenesis in both normal and obese mice, thus indicating its inhibitory role in angiogenesis, which aligns with our own findings.…”