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Angiopoietin 1 and integrin beta 1b are vital for zebrafish brain development. Frontiers in cellular neuroscience 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. 10.3389/fncel.2023.1289794
Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain. Science (New York, N.Y.) Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain. 10.1126/science.ade6970