Piezo1-Mediated Ca2+ Activities Regulate Brain Vascular Pathfinding during Development.
Neuron
; 108(1): 180-192.e5, 2020 10 14.
Article
em En
| MEDLINE
| ID: mdl-32827455
ABSTRACT
During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca2+ activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development. ETC branches display spontaneous local Ca2+ transients, and high- and low-frequency Ca2+ transients cause branch retraction through calpain and branch extension through nitric oxide synthase, respectively. These Ca2+ transients are mainly mediated by Ca2+-permeable Piezo1 channels, which can be activated by mechanical force, and mutating piezo1 largely impairs ETC pathfinding and brain vascular patterning. These findings reveal that Piezo1 and downstream Ca2+ signaling act as molecular bases for ETC pathfinding and highlight a novel function of Piezo1 and Ca2+ in vascular development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasos Sanguíneos
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Encéfalo
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Cálcio
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Neovascularização Fisiológica
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Proteínas de Peixe-Zebra
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Células Endoteliais
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Canais Iônicos
Limite:
Animals
Idioma:
En
Revista:
Neuron
Ano de publicação:
2020
Tipo de documento:
Article