A combination of members of the VEGF protein family are essential for developing brain-region specific fenestrated capillaries
Every heartbeat sends around a quarter of your blood volume to your brain, mainly via the blood-brain barrier – a network of blood vessels that don’t allow large molecules to leak out. However, certain parts of your brain have leakier blood vessels called fenestrated capillaries that do allow large molecules through. Researchers investigate how these vessels form using fluorescence microscopy of zebrafish brains with fluorescently-tagged blood vessels (pictured). They focused on signalling pathways already implicated in blood vessel development, Wnt and VEGF. Zebrafish lacking certain Wnt signalling molecules (bottom, top right) had severely disrupted blood-brain barrier vessels compared with normal brains (top left) while fenestrated capillaries were unaffected. Conversely, in zebrafish lacking different combinations of VEGF members, fenestrated blood vessels were severely disrupted. Notably, VEGFC and/or VEGFD were vital for fenestration and in certain regions, fenestration involved VEGFC interacting with VEGFA. A VEGF cocktail is, therefore, essential for developing fenestrated capillaries.
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