PUBLICATION

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

Authors

Liu, T.T., Du, X.F., Zhang, B.B., Zi, H.X., Yan, Y., Yin, J.A., Hou, H., Gu, S.Y., Chen, Q., Du, J.L.

ID

ZDB-PUB-200823-8

Date

2020

Source

Neuron 108(1): 180-192.e5 (Journal)

Registered Authors

Du, Jiu Lin

Keywords

Ca(2+) activity, Piezo1, brain vessel, calpain, endothelial tip cell, mechanical force, nitric oxide synthase, pathfinding, vascular development, zebrafish

MeSH Terms

Animals
Blood Vessels/growth & development*
Brain/blood supply*
Brain/growth & development
Calcium/metabolism*
Calcium Signaling
Calpain/metabolism
Endothelial Cells/metabolism*
Ion Channels/genetics*
Ion Channels/metabolism
Mechanotransduction, Cellular
Mutation
Neovascularization, Physiologic/genetics*
Nitric Oxide Synthase/metabolism
Zebrafish
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism

(all 17)

PubMed

32827455 Full text @ Neuron

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.

Genes / Markers

Marker	Marker Type	Name
kdrl	GENE	kinase insert domain receptor like
piezo1	GENE	piezo type mechanosensitive ion channel component 1 (Er blood group)

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
ion20dTg; s896Tg	standard conditions	Protruding-mouth	calcium-mediated signaling process quality, normal	Fig. 4
piezo1^{ion89d/ion89d}; ion20dTg; s896Tg	standard conditions	Protruding-mouth	calcium-mediated signaling decreased process quality, abnormal	Fig. 4
piezo1^{ion89d/ion89d}; s896Tg	mechanical stress, physical alteration: endothelial tip cell	Protruding-mouth	calcium-mediated signaling absent process, abnormal	Fig. 5
piezo1^{ion89d/ion89d}; s896Tg	mechanical stress, physical alteration: endothelial tip cell	Protruding-mouth	calcium-mediated signaling disrupted, abnormal	Fig. 5
piezo1^{ion89d/ion89d}; s896Tg	mechanical stress, physical alteration: endothelial tip cell	Protruding-mouth	response to mechanical stimulus absent process, abnormal	Fig. 5
piezo1^ion89d; s843Tg	standard conditions	Protruding-mouth	cranial blood vessel bent, abnormal	Fig. 6
piezo1^ion89d; s843Tg	standard conditions	Protruding-mouth	cranial blood vessel increased branchiness, abnormal	Fig. 6
piezo1^ion89d; s843Tg	standard conditions	Protruding-mouth	cranial vasculature spatial pattern, abnormal	Fig. 6
piezo1^ion89d; s843Tg	standard conditions	Protruding-mouth	sprouting angiogenesis disrupted, abnormal	Fig. 6
s843Tg	standard conditions	Protruding-mouth	cranial vasculature spatial pattern, normal	Fig. 6

1 - 10 of 12

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ion20dTg	Tg2(kdrl:GCaMP5)	Transgenic Insertion
ion89d		Small Deletion	piezo1
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
s896Tg	Tg(kdrl:Hsa.HRAS-mCherry)	Transgenic Insertion

1 - 4 of 4

Show

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
piezo1	CRISPR2-piezo1	CRISPR

Fish

Fish
ion20dTg; s896Tg
piezo1^{ion89d/ion89d}; ion20dTg
piezo1^{ion89d/ion89d}; ion20dTg; s896Tg
piezo1^{ion89d/ion89d}; s896Tg
piezo1^ion89d; s843Tg
s843Tg
s896Tg

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
AB1-piezo1	polyclonal			Goat
Ab3-tuba	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GCaMP	EFG	GCaMP
mCherry	EFG	mCherry

Mapping

Liu et al., 2020 ZDB-PUB-200823-8 PMID:32827455

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

Liu et al., 2020

ZDB-PUB-200823-8
PMID:32827455

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