PUBLICATION

Maternal Gdf3 is an obligatory cofactor in nodal signaling for embryonic axis formation in zebrafish

Authors

Bisgrove, B.W., Su, Y.C., Yost, H.J.

ID

ZDB-PUB-171117-6

Date

2017

Source

eLIFE 6: (Journal)

Registered Authors

Bisgrove, Brent, Yost, H. Joseph

Keywords

developmental biology, stem cells, zebrafish

MeSH Terms

Animals
Body Patterning*
Nodal Protein/metabolism*
Signal Transduction*
Transforming Growth Factor beta/metabolism*
Zebrafish/embryology*
Zebrafish Proteins/metabolism*

(all 7)

PubMed

29140249 Full text @ Elife

Abstract

Zebrafish Gdf3 (Dvr1) is a member of the TGFβ superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1. Signaling driven by TGFβ ligand Activin and constitutively active receptors Alk4 and Alk2 remain intact in gdf3 mutants, indicating that Gdf3 functions at the same pathway step as Nodal. Targeting gdf3 and ndr2 RNA to specific lineages indicates that exogenous gdf3 is able to fully rescue mutants only when co-expressed with endogenous Nodal. Together, these findings demonstrate that Gdf3 is an essential cofactor of Nodal signaling during establishment of the embryonic axis.

Genes / Markers

Marker	Marker Type	Name
egr2b	GENE	early growth response 2b
eve1	GENE	even-skipped-like1
foxa2	GENE	forkhead box A2
gdf3	GENE	growth differentiation factor 3
gsc	GENE	goosecoid
hand2	GENE	heart and neural crest derivatives expressed 2
lft1	GENE	lefty1
lft2	GENE	lefty2
myod1	GENE	myogenic differentiation 1
ndr1	GENE	nodal-related 1

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Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
gdf3^zy51/zy51 (AB)	standard conditions	Shield	germ ring gsc expression absent, abnormal	Fig. 3
gdf3^zy51/zy51 (AB)	standard conditions	Shield	germ ring tbxta expression spatial pattern, abnormal	Fig. 3
gdf3^zy51/zy51 (AB)	standard conditions	Shield	germ ring dorsal region tbxta expression decreased amount, abnormal	Fig. 3
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	anterior neural plate otx2b expression decreased distribution, abnormal	Fig. 2
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	axial chorda mesoderm lft1 expression absent, abnormal	Fig. 2
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	axial chorda mesoderm tbxta expression absent, abnormal	Fig. 2
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	axial hypoblast foxa2 expression absent, abnormal	Fig. 2
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	axial mesoderm anterior region ndr2 expression absent, abnormal	Fig. 2
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	axial mesoderm posterior region ndr2 expression absent, abnormal	Fig. 2
gdf3^zy51/zy51 (AB)	standard conditions	90%-epiboly	endoderm foxa2 expression absent, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
zy51	Small Deletion	gdf3
zy52	Small Deletion	gdf3
zy53	Small Deletion	gdf3

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
AB
gdf3^zy51/zy51 (AB)
gdf3^zy51/zy51 (AB)
gdf3^zy52/zy52 (AB)
gdf3^zy52/zy52 (AB)
gdf3^zy53/zy53 (AB)
gdf3^zy53/zy53 (AB)

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Bisgrove et al., 2017 ZDB-PUB-171117-6 PMID:29140249

Maternal Gdf3 is an obligatory cofactor in nodal signaling for embryonic axis formation in zebrafish

Bisgrove et al., 2017

ZDB-PUB-171117-6
PMID:29140249