PUBLICATION

Control of chemokine-guided cell migration by ligand sequestration

Authors

Boldajipour, B., Mahabaleshwar, H., Kardash, E., Reichman-Fried, M., Blaser, H., Minina, S., Wilson, D., Xu, Q., and Raz, E.

ID

ZDB-PUB-080309-8

Date

2008

Source

Cell 132(3): 463-473 (Journal)

Registered Authors

Blaser, Heiko, Boldajipour, Bijan, Kardash, Elena, Mahabaleshwar, Harsha, Minina, Sofia, Raz, Erez, Reichman-Fried, Michal, Xu, Qiling

Keywords

none

MeSH Terms

Cell Polarity
Animals, Genetically Modified
Animals
Cell Movement*
Embryo, Nonmammalian/cytology
Receptors, CXCR/genetics
Receptors, CXCR/metabolism*
Gene Expression Regulation, Developmental
Chemokine CXCL12/metabolism*
Germ Cells/cytology*
Zebrafish/embryology*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*

(all 13)

PubMed

18267076 Full text @ Cell

Abstract

Primordial germ cell (PGC) migration in zebrafish is directed by the chemokine SDF-1a that activates its receptor CXCR4b. Little is known about the molecular mechanisms controlling the distribution of this chemoattractant in vivo. We demonstrate that the activity of a second SDF-1/CXCL12 receptor, CXCR7, is crucial for proper migration of PGCs toward their targets. We show that CXCR7 functions primarily in the somatic environment rather than within the migrating cells. In CXCR7 knocked-down embryos, the PGCs exhibit a phenotype that signifies defects in SDF-1a gradient formation as the cells fail to polarize effectively and to migrate toward their targets. Indeed, somatic cells expressing CXCR7 show enhanced internalization of the chemokine suggesting that CXCR7 acts as a sink for SDF-1a, thus allowing the dynamic changes in the transcription of sdf-1a to be mirrored by similar dynamics at the protein level.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
tbx16^b104/b104	standard conditions	5-9 somites		neural rod	ISH	Fig. 6
WT	standard conditions	Shield		blastoderm	ISH	Fig. 1
WT	standard conditions	High		blastomere	ISH	Fig. 1
WT	standard conditions	20-25 somites		central nervous system	ISH	Fig. 1
WT	standard conditions	20-25 somites		hindbrain	ISH	Fig. 1
WT	standard conditions	5-9 somites		mesoderm	ISH	Fig. 1
WT	standard conditions	20-25 somites		mesoderm	ISH	Fig. 1
WT	standard conditions	5-9 somites		neural rod	ISH	Fig. 1
WT	standard conditions	5-9 somites	Not Detected	primordial germ cell	ISH	Fig. 1
WT	standard conditions	20-25 somites	Not Detected	primordial germ cell	ISH	Fig. 1

1 - 10 of 37

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: wortmannin	Prim-5	germ cell migration process quality, normal	Fig. 5
WT	chemical treatment: wortmannin	Prim-5	primordial germ cell positional polarity, normal	Fig. 5
WT + MO1-cxcr4b + MO3-cxcr4b	standard conditions	20-25 somites	germ cell migration process quality, abnormal	Fig. 2
WT + MO1-cxcr4b + MO3-cxcr4b	standard conditions	20-25 somites	primordial germ cell mislocalised, abnormal	Fig. 2
WT + MO3-ackr3b	standard conditions	20-25 somites	germ cell migration process quality, abnormal	Fig. 2
WT + MO3-ackr3b	standard conditions	20-25 somites	primordial germ cell mislocalised, abnormal	Fig. 2
er1Tg	standard conditions	Prim-5	primordial germ cell mislocalised, abnormal	Fig. 4
er1Tg + MO3-ackr3b	standard conditions	Prim-5	germ cell migration process quality, abnormal	Fig. 4
er1Tg + MO3-ackr3b	standard conditions	Prim-5	primordial germ cell cellular motility, abnormal	Fig. 4
er1Tg + MO3-ackr3b	standard conditions	Prim-5	primordial germ cell mislocalised, abnormal	Fig. 4

1 - 10 of 12

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b104		Indel	tbx16
er1Tg	Tg(kop:EGFP-FTASE-UTR-nanos3)	Transgenic Insertion
mu1Tg	Tg(kop:gra-DsRedx-UTR-nanos3)	Transgenic Insertion
t26035		Point Mutation	cxcr4b

1 - 4 of 4

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
ackr3b	MO3-ackr3b	MRPHLNO
ackr3b	MO4-ackr3b	MRPHLNO
cxcl12a	MO3-cxcl12a	MRPHLNO
cxcl12a	MO4-cxcl12a	MRPHLNO
cxcl12b	MO2-cxcl12b	MRPHLNO
cxcr4b	MO1-cxcr4b	MRPHLNO
cxcr4b	MO3-cxcr4b	MRPHLNO

1 - 7 of 7

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Fish

Fish
cxcr4b^{t26035/t26035}
er1Tg
er1Tg + MO3-ackr3b
er1Tg + MO3-cxcl12a
mu1Tg
tbx16^b104/b104
WT
WT + MO1-cxcr4b + MO3-cxcr4b
WT + MO3-ackr3b

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRedx	EFG	DsRedx
EGFP	EFG	EGFP

Mapping

Boldajipour et al., 2008 ZDB-PUB-080309-8 PMID:18267076

Control of chemokine-guided cell migration by ligand sequestration

Boldajipour et al., 2008

ZDB-PUB-080309-8
PMID:18267076