PUBLICATION

Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition

Authors

Hu, B., Gao, Y., Davies, L., Woo, S., Topczewski, J., Jessen, J.R., Lin, F.

ID

ZDB-PUB-180808-6

Date

2018

Source

Development (Cambridge, England) 145(17): (Journal)

Registered Authors

Jessen, Jason R., Lin, Fang, Topczewski, Jacek, Woo, Stephanie

Keywords

Cell migration, Endoderm, Extracellular matrix, Glypican 4, Imaging

MeSH Terms

Laminin/metabolism
Glypicans/genetics
Glypicans/metabolism*
Cell Movement/genetics
Cell Movement/physiology*
Extracellular Matrix/metabolism
Endoderm/embryology*
Pseudopodia/metabolism
Animals, Genetically Modified
Gastrulation/physiology
rac GTP-Binding Proteins/metabolism
Fibronectins/metabolism
Animals
Zebrafish/embryology*
Body Patterning/genetics
Body Patterning/physiology*
Matrix Metalloproteinase 14/genetics
Matrix Metalloproteinase 14/metabolism*

(all 18)

PubMed

30082271 Full text @ Development

Abstract

During embryogenesis, the germ layers, including the endoderm, undergo convergence and extension movements to narrow and elongate the body plan. In zebrafish, the dorsal migration of endodermal cells during gastrulation is controlled by chemokine signaling, but little is known about how they migrate during segmentation. Here, we show that glypican 4 (Gpc4), a member of the heparin sulfate proteoglycan family, is required for efficient migration of anterior endodermal cells during early segmentation, regulating Rac activation to maintain polarized actin-rich lamellipodia. An endoderm transplantation assay showed that Gpc4 regulates endoderm migration in a non-cell-autonomous fashion. Further analyses revealed that the impaired endoderm migration in gpc4 mutants results from increases in the expression and assembly of fibronectin and laminin, major components of the extracellular matrix (ECM). Notably, we found that matrix metalloproteinase 14 (Mmp14a/b) is required for the control of ECM expression during endoderm migration, with Gpc4 acting through Mmp14a/b to limit ECM expression. Our results suggest that Gpc4 is crucial for generating the environment required for efficient migration of endodermal cells, uncovering a novel function of Gpc4 during development.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	endodermal cell	IFL	Fig. 1
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	5-9 somites	endodermal cell	IFL	Fig. 1
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	Bud	endodermal cell	IHC	Fig. 5
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	endodermal cell	IHC	Fig. 5
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	5-9 somites	endodermal cell	IFL	Fig. 6
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	endodermal cell	IHC	Fig. S5
EGFP	gpc4^fr6/fr6; ha01Tg	standard conditions	Bud	endodermal cell	IHC	Fig. S5
EGFP	gpc4^fr6/fr6; ha01Tg + MO1-fn1a + MO1-lamb1a + MO4-tp53	standard conditions	5-9 somites	endodermal cell	IFL	Fig. 6
EGFP	gpc4^fr6/fr6; s944Tg; ui10Tg	standard conditions	Bud	endodermal cell lamellipodium	IFL	Fig. 2
EGFP	gpc4^fr6/fr6; s944Tg; ui10Tg	standard conditions	Bud	endodermal cell plasma membrane bounded cell projection	IFL	Fig. 2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
gpc4^fr6/fr6	standard conditions	1-4 somites	whole organism mmp14a expression decreased amount, abnormal	Fig. 8
gpc4^fr6/fr6	standard conditions	1-4 somites	whole organism mmp14b expression decreased amount, abnormal	Fig. 8
gpc4^fr6/fr6	standard conditions	Bud	whole organism mmp14b expression decreased amount, abnormal	Fig. 8
gpc4^fr6/fr6; ha01Tg	standard conditions	Bud	anatomical line ab1-lam labeling increased amount, abnormal	Fig. S5
gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	anatomical line ab1-lam labeling increased amount, abnormal	Fig. S5
gpc4^fr6/fr6; ha01Tg	standard conditions	Bud	anatomical line ab2-fn labeling increased amount, abnormal	Fig. 5
gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	anatomical line ab2-fn labeling increased amount, abnormal	Fig. 5
gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	endoderm increased width, abnormal	Fig. S8
gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites	whole organism ab2-fn labeling increased amount, abnormal	Fig. 5
gpc4^fr6/fr6; ha01Tg	standard conditions	1-4 somites to 5-9 somites	endoderm cell migration involved in gastrulation decreased efficacy, abnormal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fr6		Point Mutation	gpc4
ha01Tg	Tg(-5.0sox17:EGFP)	Transgenic Insertion
s944Tg	Tg(sox17:EGFP-Hsa.UTRN)	Transgenic Insertion
ui10Tg	Tg(sox17:H2A-mCherry)	Transgenic Insertion
ui11Tg	Tg(sox17:MA-GFP)	Transgenic Insertion
vu67		Point Mutation	vangl2

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fn1a	MO1-fn1a	MRPHLNO
lama1	MO5-lama1	MRPHLNO
lamb1a	MO1-lamb1a	MRPHLNO
lamc1	MO3-lamc1	MRPHLNO
mmp14a	MO4-mmp14a	MRPHLNO
mmp14a	MO5-mmp14a	MRPHLNO
mmp14b	MO2-mmp14b	MRPHLNO
mmp14b	MO3-mmp14b	MRPHLNO
tp53	MO4-tp53	MRPHLNO

1 - 9 of 9

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Fish

Fish
gpc4^fr6/fr6
gpc4^fr6/fr6; ha01Tg
gpc4^fr6/fr6; ha01Tg + MO1-fn1a + MO1-lamb1a + MO4-tp53
gpc4^fr6/fr6; ha01Tg + MO2-mmp14b + MO4-mmp14a + MO4-tp53
gpc4^fr6/fr6; s944Tg; ui10Tg
ha01Tg
ha01Tg + MO1-fn1a + MO1-lamb1a + MO4-tp53
ha01Tg + MO1-fn1a + MO4-tp53
ha01Tg + MO1-fn1a + MO4-tp53 + MO5-lama1
ha01Tg + MO1-lamb1a + MO4-tp53

1 - 10 of 13

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Antibodies

Name	Type	Isotypes	Host Organism
Ab1-ctnnb	monoclonal	IgG1	Mouse
Ab1-hspa9	monoclonal	IgG1	Mouse
Ab1-lam	polyclonal	IgG	Rabbit
Ab2-fn	polyclonal		Rabbit

Orthology

Engineered Foreign Genes

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

Mapping

Hu et al., 2018 ZDB-PUB-180808-6 PMID:30082271

Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition

Hu et al., 2018

ZDB-PUB-180808-6
PMID:30082271