PUBLICATION
Akt is a mediator of artery specification during zebrafish development
- Authors
- Zhou, W., Ghersi, J.J., Ristori, E., Semanchik, N., Prendergast, A., Zhang, R., Carneiro, P., Baldissera, G., Sessa, W.C., Nicoli, S.
- ID
- ZDB-PUB-240806-2
- Date
- 2024
- Source
- Development (Cambridge, England) 151(17): (Journal)
- Registered Authors
- Ghersi, Joey, Nicoli, Stefania, Prendergast, Andrew, Ristori, Emma
- Keywords
- Akt and Notch signaling, Artery specification, Endothelial cells, Single cell RNA sequencing., Vascular development, Zebrafish embryo
- Datasets
- GEO:GSE252648
- MeSH Terms
-
- Animals
- Arteries*/embryology
- Arteries*/metabolism
- Embryo, Nonmammalian/metabolism
- Endothelial Cells/metabolism
- Gene Expression Regulation, Developmental
- Mutation/genetics
- Proto-Oncogene Proteins c-akt*/genetics
- Proto-Oncogene Proteins c-akt*/metabolism
- Receptors, Notch*/genetics
- Receptors, Notch*/metabolism
- Signal Transduction
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 39101673 Full text @ Development
Citation
Zhou, W., Ghersi, J.J., Ristori, E., Semanchik, N., Prendergast, A., Zhang, R., Carneiro, P., Baldissera, G., Sessa, W.C., Nicoli, S. (2024) Akt is a mediator of artery specification during zebrafish development. Development (Cambridge, England). 151(17):.
Abstract
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. While vascular endothelial growth factor a (VEGF-A) drives 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), where expression and activity of all akt genes-akt 1, 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 reestablish 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping