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Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development
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Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development
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Journal Article
Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development
2024
Overview
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.
We investigated the effects of embryonic brain angiogenesis and neural development using qPCR,
hybridization, microangiography, retrograde labeling, and immunostaining in the
,
,
mutant fish and transgenic overexpression of
in the zebrafish larval brains.
We showed the co-localization of angpt1 with
,
, and
in the proliferation zone in the larval brain. Additionally, lack of
was associated with downregulation of
(
), and several neurogenic factors despite upregulation of
(
),
,
(
), and glial markers. We further demonstrated that the targeted
and
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
and
mutants, the
mutant fish regularly grew with no apparent phenotypes. Notably, the neural-specific
overexpression driven by the
promoter significantly increased cell proliferation and neuronal progenitor cells but decreased GABAergic neurons, and this neurogenic activity was independent of its typical receptor
.
Our results prove that
and
, 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
in embryonic neurogenesis that supports the concept of angiopoietin-based therapeutics in neurological disorders.
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