Suppression of transcytosis regulates zebrafish blood-brain barrier function

eLife

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[1] Department of Neurobiology, Harvard Medical School, Boston, United States;Department of Systems Biology, Harvard Medical School, Boston, United States;

关键词: blood-brain barrier;    development;    zebrafish;    cerebral vasculature;    Zebrafish;   

DOI  :  10.7554/eLife.47326

来源: publisher

【 摘 要 】

10.7554/eLife.47326.001As an optically transparent model organism with an endothelial blood-brain barrier (BBB), zebrafish offer a powerful tool to study the vertebrate BBB. However, the precise developmental profile of functional zebrafish BBB acquisition and the subcellular and molecular mechanisms governing the zebrafish BBB remain poorly characterized. Here, we capture the dynamics of developmental BBB leakage using live imaging, revealing a combination of steady accumulation in the parenchyma and sporadic bursts of tracer leakage. Electron microscopy studies further reveal high levels of transcytosis in brain endothelium early in development that are suppressed later. The timing of this suppression of transcytosis coincides with the establishment of BBB function. Finally, we demonstrate a key mammalian BBB regulator Mfsd2a, which inhibits transcytosis, plays a conserved role in zebrafish, as mfsd2aa mutants display increased BBB permeability due to increased transcytosis. Our findings indicate a conserved developmental program of barrier acquisition between zebrafish and mice.

【 授权许可】

CC BY