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Piezo1-Mediated Ca2+ Activities Regulate Brain Vascular Pathfinding during Development.

Ting-Ting Liu1, Xu-Fei Du2, Bai-Bing Zhang2

  • 1Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China; University of Chinese Academy of Sciences, 19A Yu-Quan Road, Beijing 100049, China.

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Summary
This summary is machine-generated.

Endothelial tip cells guide blood vessel growth. Piezo1 channels control calcium signals in these cells, regulating branch dynamics and enabling proper brain vascular development in zebrafish.

Keywords:
Ca(2+) activityPiezo1brain vesselcalpainendothelial tip cellmechanical forcenitric oxide synthasepathfindingvascular developmentzebrafish

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Area of Science:

  • Vascular biology
  • Cellular mechanotransduction
  • Developmental biology

Background:

  • Endothelial tip cells (ETCs) are crucial for guiding vascular sprouts during angiogenesis.
  • The precise mechanisms governing ETC pathfinding, essential for brain vascular patterning, are not fully understood.

Purpose of the Study:

  • To investigate the role of Piezo1-mediated calcium (Ca2+) signaling in endothelial tip cell pathfinding during zebrafish brain vascular development.

Main Methods:

  • Utilized zebrafish models to observe brain vascular development.
  • Investigated calcium transients in ETCs using live imaging.
  • Examined the effects of Piezo1 mutations and downstream signaling pathways (calpain, nitric oxide synthase) on ETC behavior and vascular patterning.

Main Results:

  • ETCs exhibit spontaneous local Ca2+ transients at primary branches.
  • High-frequency Ca2+ transients promote branch retraction via calpain.
  • Low-frequency Ca2+ transients promote branch extension via nitric oxide synthase.
  • Ca2+ transients are primarily mediated by the mechanosensitive Piezo1 channel.
  • Piezo1 dysfunction significantly impairs ETC pathfinding and brain vascular patterning.

Conclusions:

  • Piezo1-mediated Ca2+ signaling is a key regulator of endothelial tip cell branch dynamics.
  • This signaling pathway is essential for successful pathfinding and brain vascular development.
  • Highlights a novel role for Piezo1 and Ca2+ in the intricate process of vascular patterning.