PUBLICATION
Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development
- Authors
- Chen, Y.C., Martins, T.A., Marchica, V., Panula, P.
- ID
- ZDB-PUB-240118-6
- Date
- 2024
- Source
- Frontiers in Cellular Neuroscience 17: 12897941289794 (Journal)
- Registered Authors
- Chen, Yu-Chia, Panula, Pertti
- Keywords
- GABA, dopamine, histamine, hypothalamus, neurogenesis, neurovascular
- MeSH Terms
- none
- PubMed
- 38235293 Full text @ Front. Cell. Neurosci.
Citation
Chen, Y.C., Martins, T.A., Marchica, V., Panula, P. (2024) Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development. Frontiers in Cellular Neuroscience. 17:12897941289794.
Abstract
Introduction Angiopoietin 1 (angpt1) is essential for angiogenesis. However, its role in neurogenesis is largely undiscovered. This study aimed to identify the role of angpt1 in brain development, the mode of action of angpt1, and its prime targets in the zebrafish brain.
Methods We investigated the effects of embryonic brain angiogenesis and neural development using qPCR, in situ hybridization, microangiography, retrograde labeling, and immunostaining in the angpt1sa14264, itgb1bmi371, tekhu1667 mutant fish and transgenic overexpression of angpt1 in the zebrafish larval brains.
Results We showed the co-localization of angpt1 with notch, delta, and nestin in the proliferation zone in the larval brain. Additionally, lack of angpt1 was associated with downregulation of TEK tyrosine kinase, endothelial (tek), and several neurogenic factors despite upregulation of integrin beta 1b (itgb1b), angpt2a, vascular endothelial growth factor aa (vegfaa), and glial markers. We further demonstrated that the targeted angpt1sa14264 and itgb1bmi371 mutant fish showed severely irregular cerebrovascular development, aberrant hindbrain patterning, expansion of the radial glial progenitors, downregulation of cell proliferation, deficiencies of dopaminergic, histaminergic, and GABAergic populations in the caudal hypothalamus. In contrast to angpt1sa14264 and itgb1bmi371 mutants, the tekhu1667 mutant fish regularly grew with no apparent phenotypes. Notably, the neural-specific angpt1 overexpression driven by the elavl3 (HuC) promoter significantly increased cell proliferation and neuronal progenitor cells but decreased GABAergic neurons, and this neurogenic activity was independent of its typical receptor tek.
Discussion Our results prove that angpt1 and itgb1b, besides regulating vascular development, act as a neurogenic factor via notch and wnt signaling pathways in the neural proliferation zone in the developing brain, indicating a novel role of dual regulation of angpt1 in embryonic neurogenesis that supports the concept of angiopoietin-based therapeutics in neurological disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping