PUBLICATION

Sema3d controls collective endothelial cell migration by distinct mechanisms via Nrp1 and PlxnD1

Authors

Hamm, M.J., Kirchmaier, B.C., Herzog, W.

ID

ZDB-PUB-161102-8

Date

2016

Source

The Journal of cell biology 215(3): 415-430 (Journal)

Registered Authors

Herzog, Wiebke, Kirchmaier, Bettina

Keywords

none

MeSH Terms

Pseudopodia/metabolism
Cell Movement*
Animals
Nerve Growth Factors/metabolism*
Blood Vessels/cytology
Blood Vessels/embryology
Signal Transduction
Cadherins/metabolism
rhoA GTP-Binding Protein/metabolism
Neuropilin-1/metabolism*
Endothelial Cells/cytology*
Endothelial Cells/metabolism*
Mesoderm/cytology
Mesoderm/metabolism
Zebrafish/embryology
Zebrafish/metabolism*
Models, Biological
Receptors, Cell Surface/metabolism*
Zebrafish Proteins/metabolism*
Actins/metabolism
Cell Shape
Cell Communication
Semaphorins/metabolism*

(all 23)

PubMed

27799363 Full text @ J. Cell Biol.

Abstract

During cardiovascular development, tight spatiotemporal regulation of molecular cues is essential for controlling endothelial cell (EC) migration. Secreted class III Semaphorins play an important role in guidance of neuronal cell migration and were lately linked to regulating cardiovascular development. Recently, SEMA3D gene disruptions were associated with cardiovascular defects in patients; however, the mechanisms of action were not revealed. Here we show for the first time that Sema3d regulates collective EC migration in zebrafish through two separate mechanisms. Mesenchymal Sema3d guides outgrowth of the common cardinal vein via repulsion and signals through PlexinD1. Additionally, within the same ECs, we identified a novel function of autocrine Sema3d signaling in regulating Actin network organization and EC morphology. We show that this new function requires Sema3d signaling through Neuropilin1, which then regulates Actin network organization through RhoA upstream of Rock, stabilizing the EC sheet. Our findings are highly relevant for understanding EC migration and the mechanisms of collective migration in other contexts.

Genes / Markers

Figures

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Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
cdh5	ab1-cdh5	WT	control	Prim-15	common cardinal vein cell-cell junction	IHC	Fig. 6
cdh5		WT	standard conditions	Prim-15	common cardinal vein	ISH	Fig. 7
cdh5	ab1-cdh5	WT + MO2-sema3d	standard conditions	Prim-15	common cardinal vein cell-cell junction	IHC	Fig. 6
EGFP		cdh5^ubs8/ubs8; mu240Tg	standard conditions	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 6
EGFP		mu240Tg	chemical treatment by environment: latrunculin A	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 5
EGFP		mu240Tg	chemical treatment by environment: (S)-2-methyl-1-(4-methylisoquinoline-5-sulfonyl)-1,4-diazepane	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 5
EGFP		mu240Tg	control	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 5
EGFP		mu240Tg	chemical treatment by environment: blebbistatin	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 5
EGFP		mu240Tg	standard conditions	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 6
EGFP		mu240Tg	control	Prim-15	common cardinal vein blood vessel endothelium	IFL	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-sema3d	standard conditions	Prim-15	common cardinal vein cell-cell junction cdh5 expression spatial pattern, abnormal	Fig. 6
WT + MO2-sema3d	standard conditions	Prim-15	common cardinal vein cell-cell junction decreased length, abnormal	Fig. 6
WT + MO2-sema3d	standard conditions	Prim-15	common cardinal vein cell-cell junction irregular spatial pattern, abnormal	Fig. 6
cdh5^ubs8/ubs8; mu240Tg	standard conditions	Prim-15	common cardinal vein blood vessel endothelial cell structure, cavities, abnormal	Fig. 6
cdh5^ubs8/ubs8; mu240Tg	standard conditions	Prim-15	common cardinal vein cell-cell junction length, normal	Fig. 6
mu240Tg	chemical treatment by environment: blebbistatin	Prim-15	common cardinal vein blood vessel endothelium patchy, abnormal	Fig. 5
mu240Tg	chemical treatment by environment: blebbistatin	Prim-15	common cardinal vein width, normal	Fig. 5
mu240Tg	chemical treatment by environment: latrunculin A	Prim-15	common cardinal vein blood vessel endothelium patchy, abnormal	Fig. 5
mu240Tg	chemical treatment by environment: latrunculin A	Prim-15	common cardinal vein width, normal	Fig. 5
mu240Tg	chemical treatment by environment: nifedipine, chemical treatment by environment: tricaine	Prim-15	common cardinal vein cell-cell junction length, normal	Fig. 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hu5088		Point Mutation	kdrl
hu10012		Small Deletion	nrp1a
mu240Tg	Tg3(fli1:LIFEACT-EGFP)	Transgenic Insertion
mu268		Small Deletion	sema3d
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
s896Tg	Tg(kdrl:Hsa.HRAS-mCherry)	Transgenic Insertion
ubs8		Small Deletion	cdh5
uw14Tg	Tg(hsp70l:sema3d-GFP)	Transgenic Insertion
zf106Tg	Tg(-8.0cldnb:LY-EGFP)	Transgenic Insertion

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
kdrl	MO1-kdrl	MRPHLNO
nrp1a	MO1-nrp1a	MRPHLNO
nrp1a	MO2-nrp1a	MRPHLNO
plxnd1	MO2-plxnd1	MRPHLNO
sema3d	CRISPR1-sema3d	CRISPR
sema3d	MO2-sema3d	MRPHLNO
sema3d	MO6-sema3d	MRPHLNO
vegfaa	MO3-vegfaa	MRPHLNO
vegfab	MO1-vegfab	MRPHLNO

1 - 9 of 9

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Fish

Fish
cdh5^ubs8/ubs8; mu240Tg
mu240Tg
mu240Tg + MO1-nrp1a
mu240Tg + MO2-nrp1a
mu240Tg + MO2-plxnd1
mu240Tg + MO2-sema3d
nrp1a^{hu10012/hu10012}; s843Tg
s843Tg
s843Tg + MO2-plxnd1
s843Tg + MO2-sema3d

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-cdh5		cdh5		Rabbit
Ab1-sema3d	polyclonal	sema3d		Rabbit
Ab1-tjp1	monoclonal	tjp1a tjp1b	IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Hamm et al., 2016 ZDB-PUB-161102-8 PMID:27799363

Sema3d controls collective endothelial cell migration by distinct mechanisms via Nrp1 and PlxnD1

Hamm et al., 2016

ZDB-PUB-161102-8
PMID:27799363