PUBLICATION

Directional migration of neural crest cells in vivo is regulated by Syndecan-4/Rac1 and non-canonical Wnt signaling/RhoA

Authors

Matthews, H.K., Marchant, L., Carmona-Fontaine, C., Kuriyama, S., Larraín, J., Holt, M.R., Parsons, M., and Mayor, R.

ID

ZDB-PUB-080415-10

Date

2008

Source

Development (Cambridge, England) 135(10): 1771-1780 (Journal)

Registered Authors

Mayor, Roberto

Keywords

Cell migration, Neural crest, Directionality, Persistence, Syndecan-4, Non-canonical Wnt signaling, PCP, RhoA, Rac1

MeSH Terms

Cell Polarity/physiology
Syndecan-4/biosynthesis
Syndecan-4/physiology*
rac1 GTP-Binding Protein/physiology*
Fluorescence Resonance Energy Transfer
Animals
Wnt Proteins/physiology*
Neural Crest/cytology*
Neural Crest/embryology
Neural Crest/metabolism
Signal Transduction
rhoA GTP-Binding Protein/physiology*
Cell Movement/physiology
cdc42 GTP-Binding Protein/metabolism
Xenopus
Zebrafish
Embryo, Nonmammalian/physiology

(all 17)

PubMed

18403410 Full text @ Development

Abstract

Directed cell migration is crucial for development, but most of our current knowledge is derived from in vitro studies. We analyzed how neural crest (NC) cells migrate in the direction of their target during embryonic development. We show that the proteoglycan Syndecan-4 (Syn4) is expressed in the migrating neural crest of Xenopus and zebrafish embryos. Loss-of-function studies using an antisense morpholino against syn4 show that this molecule is required for NC migration, but not for NC induction. Inhibition of Syn4 does not affect the velocity of cell migration, but significantly reduces the directional migration of NC cells. Furthermore, we show that Syn4 and PCP signaling control the directional mfor NC migration, but not for NC induction. Inhibition of Syn4 does not affect the velocity of cell migration, but significantly reduces the direigration of NC cells by regulating the direction in which the cell protrusions are generated during migration. Finally, we perform FRET analysis of Cdc42, Rac and RhoA in vitro and in vivo after interfering with Syn4 and PCP signaling. This is the first time that FRET analysis of small GTPases has been performed in vivo. Our results show that Syn4 inhibits Rac activity, whereas PCP signaling promotes RhoA activity. In addition, we show that RhoA inhibits Rac in NC cells. We present a model in which Syn4 and PCP control directional NC migration by, at least in part, regulating membrane protrusions through the regulation of small GTPase activities.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
crestin	vangl2^{unspecified/unspecified}	standard conditions	20-25 somites	neural crest	ISH	Fig. 7
crestin	vangl2^{unspecified/unspecified} + MO1-sdc4	standard conditions	20-25 somites	neural crest	ISH	Fig. 7
crestin	WT	standard conditions	20-25 somites	neural crest	ISH	Fig. 1
crestin	WT	standard conditions	20-25 somites	neural crest	ISH	Fig. 7
crestin	WT + MO1-sdc4	standard conditions	20-25 somites	neural crest	ISH	Fig. 7
crestin	WT + MO1-sdc4 + MO1-wnt5b	standard conditions	20-25 somites	neural crest	ISH	Fig. 7
crestin	WT + MO1-wnt5b	standard conditions	20-25 somites	neural crest	ISH	Fig. 7
EGFP	ba2Tg	control	Day 5	cranial cartilage	IFL	Fig. 2
EGFP	ba2Tg	control	Prim-5	neural crest	IFL	Fig. S3
EGFP	ba2Tg	control	14-19 somites	neural crest	IFL	Fig. 6

1 - 10 of 18

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-sdc4	standard conditions	20-25 somites	neural crest cell migration disrupted, abnormal	Fig. 3
WT + MO1-sdc4	standard conditions	Prim-5	melanocyte decreased amount, abnormal	Fig. 2
WT + MO1-sdc4	standard conditions	Prim-5	melanocyte differentiation disrupted, abnormal	Fig. 2
WT + MO1-sdc4	standard conditions	Day 5	cartilage development disrupted, abnormal	Fig. 2
WT + MO1-sdc4	standard conditions	Day 5	cranial cartilage morphology, abnormal	Fig. 2
WT + MO1-sdc4	standard conditions	Day 5	neural crest formation disrupted, abnormal	Fig. 2
ba2Tg + MO2-sdc4	standard conditions	Day 5	cartilage development disrupted, abnormal	Fig. 2
ba2Tg + MO2-sdc4	standard conditions	Day 5	cranial cartilage morphology, abnormal	Fig. 2
ba2Tg + MO2-sdc4	standard conditions	Day 5	neural crest formation disrupted, abnormal	Fig. 2

1 - 9 of 9

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ba2Tg	Tg(-4.9sox10:EGFP)	Transgenic Insertion
vangl2_unspecified		Unspecified	vangl2

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
sdc4	MO1-sdc4	MRPHLNO
sdc4	MO2-sdc4	MRPHLNO
wnt5b	MO1-wnt5b	MRPHLNO

Fish

Fish
ba2Tg
ba2Tg + MO1-sdc4
ba2Tg + MO2-sdc4
vangl2^{unspecified/unspecified}
vangl2^{unspecified/unspecified} + MO1-sdc4
WT
WT + MO1-sdc4
WT + MO1-sdc4 + MO1-wnt5b
WT + MO1-wnt5b

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Matthews et al., 2008 ZDB-PUB-080415-10 PMID:18403410

Directional migration of neural crest cells in vivo is regulated by Syndecan-4/Rac1 and non-canonical Wnt signaling/RhoA

Matthews et al., 2008

ZDB-PUB-080415-10
PMID:18403410