Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development.

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, hybridization, microangiography, retrograde labeling, and immunostaining in the , , mutant fish and transgenic overexpression of in the zebrafish larval brains.

RESULTS

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 .

DISCUSSION

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.