Akt is a mediator of artery specification during zebrafish development.

Autor:	Zhou W; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, USA.; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA., Ghersi JJ; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.; Pathologies Foetomaternelles et Néonatales, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada.; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada., Ristori E; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA., Semanchik N; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Prendergast A; Department of Comparative Medicine, Yale zebrafish Research Core, Yale University School of Medicine, New Haven, CT 06510, USA., Zhang R; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA., Carneiro P; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Baldissera G; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Sessa WC; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA., Nicoli S; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Sep 01; Vol. 151 (17). Date of Electronic Publication: 2024 Sep 02.
DOI:	10.1242/dev.202727
Abstrakt:	The dorsal aorta (DA) is the first major blood vessel to develop in the embryonic cardiovascular system. Its formation is governed by a coordinated process involving the migration, specification, and arrangement of angioblasts into arterial and venous lineages, a process conserved across species. Although vascular endothelial growth factor a (VEGF-A) is known to drive DA specification and formation, the kinases involved in this process remain ambiguous. Thus, we investigated the role of protein kinase B (Akt) in zebrafish by generating a quadruple mutant (aktΔ/Δ), in which expression and activity of all Akt genes - akt1, -2, -3a and -3b - are strongly decreased. Live imaging of developing aktΔ/Δ DA uncovers early arteriovenous malformations. Single-cell RNA-sequencing analysis of aktΔ/Δ endothelial cells corroborates the impairment of arterial, yet not venous, cell specification. Notably, endothelial specific expression of ligand-independent activation of Notch or constitutively active Akt1 were sufficient to re-establish normal arterial specification in aktΔ/Δ. The Akt loss-of-function mutant unveils that Akt kinase can act upstream of Notch in arterial endothelial cells, and is involved in proper embryonic artery specification. This sheds light on cardiovascular development, revealing a mechanism behind congenital malformations. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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