PUBLICATION

Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction

Authors

Paatero, I., Sauteur, L., Lee, M., Lagendijk, A.K., Heutschi, D., Wiesner, C., Guzmán, C., Bieli, D., Hogan, B.M., Affolter, M., Belting, H.G.

ID

ZDB-PUB-190117-8

Date

2018

Source

Nature communications 9: 3545 (Journal)

Registered Authors

Affolter, Markus, Belting, Heinz-Georg Paul (Henry), Hogan, Ben M., Paatero, Ilkka, Sauteur, Loïc

Keywords

none

MeSH Terms

Pseudopodia/physiology*
Cell Movement/physiology*
Cadherins/physiology*
Endothelial Cells/physiology*
Antigens, CD/physiology*
Embryo, Nonmammalian
Actins/metabolism*
Zonula Occludens-1 Protein/metabolism
Zebrafish Proteins/metabolism
Animals, Genetically Modified
Animals
Cell Communication/physiology
Intercellular Junctions/physiology

(all 13)

PubMed

30171187 Full text @ Nat. Commun.

Abstract

Angiogenesis and vascular remodeling are driven by extensive endothelial cell movements. Here, we present in vivo evidence that endothelial cell movements are associated with oscillating lamellipodia-like structures, which emerge from cell junctions in the direction of cell movements. High-resolution time-lapse imaging of these junction-based lamellipodia (JBL) shows dynamic and distinct deployment of junctional proteins, such as F-actin, VE-cadherin and ZO1, during JBL oscillations. Upon initiation, F-actin and VE-cadherin are broadly distributed within JBL, whereas ZO1 remains at cell junctions. Subsequently, a new junction is formed at the front of the JBL, which then merges with the proximal junction. Rac1 inhibition interferes with JBL oscillations and disrupts cell elongation-similar to a truncation in ve-cadherin preventing VE-cad/F-actin interaction. Taken together, our observations suggest an oscillating ratchet-like mechanism, which is used by endothelial cells to move over each other and thus provides the physical means for cell rearrangements.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	s843Tg	standard conditions	Prim-5	blood vessel endothelial cell	IHC	Fig. 1
EGFP	ubs18Tg; ubs3Tg	standard conditions	Long-pec	blood vessel endothelial cell cell-cell junction	IFL	Fig. 3
EGFP	ubs18Tg; ubs3Tg	standard conditions	Long-pec	blood vessel endothelial cell lamellipodium	IFL	Fig. 3
EGFP	ubs18Tg; ubs3Tg	standard conditions	Prim-15	blood vessel endothelial cell lamellipodium	IFL	Fig. 2
EGFP	ubs20Tg; ubs3Tg; ubs5Tg	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction	IFL	Fig. 5
mClavGR2	ubs27Tg; ubs3Tg	control	Prim-15	blood vessel endothelial cell cell-cell junction	IFL	Fig. 4
mClavGR2	ubs27Tg; ubs3Tg	control	Prim-15	blood vessel endothelial cell lamellipodium	IFL	Fig. 4
mRuby	ubs20Tg; ubs3Tg; ubs5Tg	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction	IFL	Fig. 5
mRuby	ubs20Tg; ubs3Tg; uq11bhTg	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction	IFL	Fig. 5
Venus	ubs20Tg; ubs3Tg; uq11bhTg	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction	IFL	Fig. 5

1 - 10 of 12

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
cdh5^ubs25/ubs25	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction ab1-tjp1 labeling decreased amount, abnormal	Fig. 7
cdh5^ubs25/ubs25	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction ab1-tjp1 labeling decreased distribution, abnormal	Fig. 7
cdh5^ubs25/ubs25	standard conditions	Long-pec	blood circulation decreased occurrence, abnormal	Fig. S5
cdh5^ubs25/ubs25	standard conditions	Long-pec	pericardium edematous, abnormal	Fig. S5
cdh5^ubs25/ubs25; s843Tg	standard conditions	Long-pec	posterior cardinal vein increased size, abnormal	Fig. S5
cdh5^ubs25/ubs25; ubs18Tg; ubs3Tg	standard conditions	Prim-15	blood vessel endothelial cell cell-cell junction organization process quality, abnormal	Fig. 7
cdh5^ubs25/ubs25; ubs18Tg; ubs3Tg	standard conditions	Prim-15	dorsal longitudinal anastomotic vessel cell-cell junction organization process quality, abnormal	Fig. 7
cdh5^ubs25/ubs25; ubs18Tg; ubs3Tg	standard conditions	Long-pec	endothelial tip cell separated from blood vessel endothelial cell, abnormal	Fig. S5
cdh5^ubs25/ubs25; ubs18Tg; ubs3Tg	standard conditions	Long-pec	intersegmental vessel disconnected, abnormal	Fig. S5
cdh5^ubs25/ubs25; ubs1Tg	standard conditions	Prim-15	intersegmental vessel blood vessel morphogenesis process quality, abnormal	Fig. 7

1 - 10 of 19

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
nkuasrfp1aTg	Tg(5xUAS:RFP)	Transgenic Insertion
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
ubs1Tg	Tg(kdrl:NLS-EGFP)	Transgenic Insertion
ubs3Tg	Tg(fli1:GAL4FF)	Transgenic Insertion
ubs5Tg	Tg(14xUAS:EGFP-Hsa.TJP1,myl7:EGFP)	Transgenic Insertion
ubs8		Small Deletion	cdh5
ubs18Tg	Tg(4xUAS:Hsa.UTRN-EGFP)	Transgenic Insertion
ubs20Tg	Tg(4xUAS:mRuby-Hsa.UTRN)	Transgenic Insertion
ubs25		Small Deletion	cdh5
ubs27Tg	Tg(4xUAS:mClavGR2-Hsa.UTRN)	Transgenic Insertion

1 - 10 of 11

Show

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cdh5	CRISPR4-cdh5	CRISPR

Fish

Fish
cdh5^ubs8/ubs8
cdh5^ubs25/ubs25
cdh5^ubs25/ubs25; s843Tg
cdh5^ubs25/ubs25; ubs1Tg
cdh5^ubs25/ubs25; ubs18Tg; ubs3Tg
s843Tg
ubs3Tg; ubs5Tg
ubs18Tg; ubs3Tg
ubs20Tg; ubs3Tg; ubs5Tg
ubs20Tg; ubs3Tg; uq11bhTg

1 - 10 of 13

Show

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4FF	EFG	GAL4FF
mClavGR2	EFG	mClavGR2
mRuby	EFG	mRuby
RFP	EFG	RFP
TENS	EFG	TENS
TFP	EFG	TFP
Venus	EFG	Venus

Mapping

Paatero et al., 2018 ZDB-PUB-190117-8 PMID:30171187

Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction

Paatero et al., 2018

ZDB-PUB-190117-8
PMID:30171187