PUBLICATION

The epithelial cell adhesion molecule EpCAM is required for epithelial morphogenesis and integrity during zebrafish epiboly and skin development

Authors

Slanchev, K., Carney, T.J., Stemmler, M.P., Koschorz, B., Amsterdam, A., Schwarz, H., and Hammerschmidt, M.

ID

ZDB-PUB-090720-6

Date

2009

Source

PLoS Genetics 5(7): e1000563 (Journal)

Registered Authors

Amsterdam, Adam, Carney, Tom, Hammerschmidt, Matthias, Slanchev, Krasimir

Keywords

Embryos, Zebrafish, Keratinocytes, Basal cells, Cell staining, Morphogenesis, Tight junctions, Cell differentiation

MeSH Terms

Animals
Antigens, Neoplasm/physiology*
Cadherins/physiology
Cell Adhesion
Cell Adhesion Molecules/physiology*
Embryo, Nonmammalian
Epithelium/embryology
Epithelium/growth & development*
Membrane Glycoproteins/physiology*
Morphogenesis*
Skin/embryology
Skin/growth & development*
Zebrafish
Zebrafish Proteins/physiology*

(all 14)

PubMed

19609345 Full text @ PLoS Genet.

Abstract

The aberrant expression of the transmembrane protein EpCAM is associated with tumor progression, affecting different cellular processes such as cell-cell adhesion, migration, proliferation, differentiation, signaling, and invasion. However, the in vivo function of EpCAM still remains elusive due to the lack of genetic loss-of-function studies. Here, we describe epcam (tacstd) null mutants in zebrafish. Maternal-zygotic mutants display compromised basal protrusive activity and epithelial morphogenesis in cells of the enveloping layer (EVL) during epiboly. In partial redundancy with E-cadherin (Ecad), EpCAM made by EVL cells is further required for cell-cell adhesion within the EVL and, possibly, for proper attachment of underlying deep cells to the inner surface of the EVL, thereby also affecting deep cell epiboly movements. During later development, EpCAM per se becomes indispensable for epithelial integrity within the periderm of the skin, secondarily leading to disrupted morphology of the underlying basal epidermis and moderate hyper-proliferation of skin cells. On the molecular level, EVL cells of epcam mutant embryos display reduced levels of membranous Ecad, accompanied by an enrichment of tight junction proteins and a basal extension of apical junction complexes (AJCs). Our data suggest that EpCAM acts as a partner of E-cadherin to control adhesiveness and integrity as well as plasticity and morphogenesis within simple epithelia. In addition, EpCAM is required for the interaction of the epithelia with underlying cell layers.

Genes / Markers

Marker	Marker Type	Name
cdh1	GENE	cadherin 1, type 1, E-cadherin (epithelial)
epcam	GENE	epithelial cell adhesion molecule
lcp1	GENE	lymphocyte cytosolic protein 1 (L-plastin)
tjp1a	GENE	tight junction protein 1a
tnika	GENE	TRAF2 and NCK interacting kinase a

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Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-epcam	standard conditions	Day 5	keratinocyte aggregated, abnormal	Fig. 1
WT + MO2-epcam	standard conditions	Day 5	otolith decreased size, abnormal	Fig. 1
epcam^{hi2151Tg/hi2151Tg}	standard conditions	75%-epiboly	EVL ruffle absent, abnormal	Fig. 6
epcam^{hi2151Tg/hi2151Tg}	standard conditions	90%-epiboly	apical junction assembly disrupted, abnormal	Fig. 7
epcam^{hi2151Tg/hi2151Tg}	standard conditions	90%-epiboly	epiboly involved in gastrulation with mouth forming second disrupted, abnormal	Fig. 5
epcam^{hi2151Tg/hi2151Tg}	standard conditions	90%-epiboly	yolk protruding out of whole organism, abnormal	Fig. 5
epcam^{hi2151Tg/hi2151Tg}	standard conditions	14-19 somites	tail bud integument aggregated, abnormal	Fig. 3
epcam^{hi2151Tg/hi2151Tg}	standard conditions	Prim-5	cell population proliferation increased rate, abnormal	Fig. 4
epcam^{hi2151Tg/hi2151Tg}	standard conditions	Prim-25	keratinocyte aggregated, abnormal	Fig. 3
epcam^{hi2151Tg/hi2151Tg}	standard conditions	Long-pec	apical junction assembly disrupted, abnormal	Fig. 7

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
gz7Tg	Tg(krt4:GFP)	Transgenic Insertion
hi2151Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	epcam
hi2836Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	epcam
vu119Tg	Tg(Ola.Actb:Hsa.HRAS-EGFP)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cdh1	MO3-cdh1	MRPHLNO
epcam	MO2-epcam	MRPHLNO
tnika	MO1-tnika	MRPHLNO

Fish

Fish
epcam^{hi2151Tg/hi2151Tg}
epcam^{hi2151Tg/hi2151Tg} + MO3-cdh1
epcam^{hi2836Tg/hi2836Tg}
gz7Tg
vu119Tg
WT
WT + MO2-epcam

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Slanchev et al., 2009 ZDB-PUB-090720-6 PMID:19609345

The epithelial cell adhesion molecule EpCAM is required for epithelial morphogenesis and integrity during zebrafish epiboly and skin development

Slanchev et al., 2009

ZDB-PUB-090720-6
PMID:19609345