PUBLICATION

Sfrp5 Modulates Both Wnt and BMP Signaling and Regulates Gastrointestinal Organogensis in the Zebrafish, Danio rerio

Authors

Stuckenholz, C., Lu, L., Thakur, P.C., Choi, T.Y., Shin, D., and Bahary, N.

ID

ZDB-PUB-130605-16

Date

2013

Source

PLoS One 8(4): e62470 (Journal)

Registered Authors

Bahary, Nathan, Choi, Tae-Young, Shin, Donghun, Stuckenholz, Carsten, Thakur, Prakash Chandra

Keywords

none

MeSH Terms

Animals
Organogenesis*
Fertilization
Wnt Proteins/metabolism*
Signal Transduction*
Intercellular Signaling Peptides and Proteins/deficiency
Intercellular Signaling Peptides and Proteins/genetics
Intercellular Signaling Peptides and Proteins/metabolism*
Endoderm/metabolism
Organ Size
Phenotype
Bone Morphogenetic Proteins/metabolism*
Liver/embryology
Liver/metabolism
Islets of Langerhans/embryology
Islets of Langerhans/metabolism
Zebrafish/embryology*
Zebrafish Proteins/deficiency
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Embryo, Nonmammalian/embryology
Embryo, Nonmammalian/metabolism
Embryo, Nonmammalian/physiology
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Tolloid-Like Metalloproteinases/antagonists & inhibitors
Gastrointestinal Tract/embryology*

(all 27)

PubMed

23638093 Full text @ PLoS One

Abstract

Sfrp5 belongs to the family of secreted frizzled related proteins (Sfrp), secreted inhibitors of Wingless-MMTV Integration Site (Wnt) signaling, which play an important role in cancer and development. We selected sfrp5 because of its compelling expression profile in the developing endoderm in zebrafish, Danio rerio. In this study, overexpression of sfrp5 in embryos results in defects in both convergent extension (CE) by inhibition of non-canonical Wnt signaling and defects in dorsoventral patterning by inhibition of Tolloid-mediated proteolysis of the BMP inhibitor Chordin. From 25 hours post fertilization (hpf) to 3 days post fertilization (dpf), both overexpression and knockdown of Sfrp5 decrease the size of the endoderm, significantly reducing liver cell number. At 3 dpf, insulin-positive endodermal cells fail to coalesce into a single pancreatic islet. We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities.

Genes / Markers

Figures

Show all Figures

Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
WT	control	Protruding-mouth	intestine	ISH	Fig. 7
WT + MO1-sfrp5	standard conditions	Protruding-mouth	intestine	ISH	Fig. 7
WT	control	Protruding-mouth	liver	ISH	Fig. 7
WT + MO1-sfrp5	standard conditions	Protruding-mouth	liver	ISH	Fig. 7
WT	control	Prim-25	endoderm	ISH	Fig. 6
WT	control	Prim-5	endoderm	ISH	Fig. 6
WT	control	Long-pec	endoderm	ISH	Fig. 6
WT + MO1-sfrp5	standard conditions	Prim-5	endoderm	ISH	Fig. 6
WT + MO1-sfrp5	standard conditions	Prim-25	endoderm	ISH	Fig. 6
WT + MO1-sfrp5	standard conditions	Long-pec	endoderm	ISH	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-sfrp5	standard conditions	Prim-5	endoderm decreased size, abnormal	Fig. 6
WT + MO1-sfrp5	standard conditions	Prim-5	hepatoblast decreased size, abnormal	Fig. 5
WT + MO1-sfrp5	standard conditions	Prim-25	endoderm decreased size, abnormal	Fig. 6
WT + MO1-sfrp5	standard conditions	Prim-25	hepatoblast decreased size, abnormal	Fig. 5
WT + MO1-sfrp5	standard conditions	Long-pec	endoderm decreased size, abnormal	Fig. 6
WT + MO1-sfrp5	standard conditions	Long-pec	hepatoblast decreased size, abnormal	Fig. 5
WT + MO1-sfrp5	standard conditions	Protruding-mouth	intestine decreased size, abnormal	Fig. 7
WT + MO1-sfrp5	standard conditions	Protruding-mouth	liver decreased size, abnormal	Fig. 7
WT + MO1-sfrp5	standard conditions	Protruding-mouth	pancreas decreased size, abnormal	Fig. 7
s854Tg + MO1-sfrp5	standard conditions	Long-pec	liver decreased size, abnormal	Fig. 5

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
pt603Tg	Tg(hsp70l:mCherry,wnt2bb,cryaa:ECFP)	Transgenic Insertion
s854Tg	Tg(Xla.Eef1a1:GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
sfrp5	MO1-sfrp5	MRPHLNO

Fish

Fish
pt603Tg/+ (AB)
s854Tg
s854Tg + MO1-sfrp5
WT
WT + MO1-sfrp5

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
ECFP	EFG	ECFP
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Stuckenholz et al., 2013 ZDB-PUB-130605-16 PMID:23638093

Sfrp5 Modulates Both Wnt and BMP Signaling and Regulates Gastrointestinal Organogensis in the Zebrafish, Danio rerio

Stuckenholz et al., 2013

ZDB-PUB-130605-16
PMID:23638093