Function of Piezo1 and Ca2+ in Brain Vascular Development Explained

A team of researchers from the Chinese Academy of Sciences reported today in Neuron that Ca²⁺ activities mediated by mechanosensitive Piezo1 channels regulate the pathfinding of growing brain vessels in larval zebrafish. Their work helps shed light on the mechanisms behind the patterning of brain vasculature during development.

To investigate the cellular and molecular mechanism underlying endothelial tip cells (ETC) pathfinding, a team led by Du Jiulin first monitored the entire process of ETC pathfinding during brain vascular development through in vivo long-term time-lapse simultaneous imaging of both the morphological dynamics and Ca²⁺ activity of ETCs in larval zebrafish. They found that before reaching target vessels, ETCs frequently extended and retracted subcellular primary branches, leading to continuous changes in the direction of ETC migration and vessel growth.

Then the researchers examined the causal relationship between local Ca²⁺ transients and fate determination of ETC branches via local manipulation of Ca²⁺ concentration at ETC branches, and found that high- and low-frequency Ca²⁺ transients were necessary and sufficient for the retraction and extension of ETC branches, respectively.

Furthermore, they investigated the origin of local Ca²⁺ activities of ETCs, and discovered that mechanosensitive Piezo1 cationic channels were preferentially expressed on ETC branches and activated by tissue stiffness-associated mechanical force. "They mediated local Ca²⁺ activities of ETC branches, thus regulating the retraction and extension of ETC branches," explained Du.

In addition, mutating piezo1 largely diminished local Ca²⁺ transients of ETC branches, impaired the pathfinding of ETCs, and therefore disrupted the patterning of the brain vasculature.