PUBLICATION

Multiple roles for Med12 in vertebrate endoderm development

Authors

Shin, C.H., Chung, W.S., Hong, S.K., Ober, E.A., Verkade, H., Field, H.A., Huisken, J., and Stainier, D.Y.

ID

ZDB-PUB-080414-12

Date

2008

Source

Developmental Biology 317(2): 467-479 (Journal)

Registered Authors

Chung, Won-Suk, Hong, Sung-Kook, Ober, Elke, Shin, Chong, Stainier, Didier, Verkade, Heather

Keywords

none

MeSH Terms

DNA Primers/genetics
High Mobility Group Proteins/metabolism
DNA-Binding Proteins/metabolism
SOXF Transcription Factors
Polymorphism, Restriction Fragment Length/genetics
Basic Helix-Loop-Helix Transcription Factors/metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Molecular Sequence Data
Mutagenesis
Animals
Transcription Factors/genetics
Transcription Factors/metabolism*
Base Sequence
Phenotype*
Endoderm/embryology*
Endoderm/metabolism
Gene Expression Regulation, Developmental*
Sequence Analysis, DNA
Cell Differentiation/physiology*
Mediator Complex
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Cell Line
Vertebrates/embryology*
In Situ Nick-End Labeling

(all 25)

PubMed

18394596 Full text @ Dev. Biol.

Abstract

In zebrafish, the endoderm originates at the blastula stage from the most marginal blastomeres. Through a series of complex morphogenetic movements and differentiation events, the endodermal germ layer gives rise to the epithelial lining of the digestive tract as well as its associated organs such as the liver, pancreas, and swim bladder. How endodermal cells differentiate into distinct cell types such as hepatocytes or endocrine and exocrine pancreatic cells remains a major question. In a forward genetic screen for genes regulating endodermal organ development, we identified mutations at the shiri locus that cause defects in the development of a number of endodermal organs including the liver and pancreas. Detailed phenotypic analyses indicate that these defects are partially due to a reduction in endodermal expression of the hairy/enhancer of split-related gene, her5, at mid to late gastrulation stages. Using the Tg(0.7her5:EGFP)(ne2067) line, we show that her5 is expressed in the endodermal precursors that populate the pharyngeal region as well as the organ-forming region. We also find that knocking down her5 recapitulates some of the endodermal phenotypes of shiri mutants, further revealing the role of her5 in endoderm development. Positional cloning reveals that shiri encodes Med12, a regulatory subunit of the transcriptional Mediator complex recently associated with two human syndromes. Additional studies indicate that Med12 modulates the ability of Casanova/Sox32 to induce sox17 expression. Thus, detailed phenotypic analyses of embryos defective in a component of the Mediator complex have revealed new insights into discrete aspects of vertebrate endoderm development, and provide possible explanations for the craniofacial and digestive system defects observed in humans with mutations in MED12.

Genes / Markers

Figures

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Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
alcama	zn-5	med12^s435/s435; s854Tg	standard conditions	Protruding-mouth	liver	IHC	Fig. 1
alcama	zn-5	med12^s435/s435; s854Tg	standard conditions	Long-pec	liver	IHC	Fig. 1
alcama	zn-5	med12^s435/s435; s854Tg	standard conditions	Protruding-mouth	pancreas	IHC	Fig. 1
alcama	zn-5	med12^s435/s435; s854Tg	standard conditions	Long-pec	pancreas	IHC	Fig. 1
alcama	zn-5	s854Tg	standard conditions	Long-pec	liver	IHC	Fig. 1
alcama	zn-5	s854Tg	standard conditions	Protruding-mouth	liver	IHC	Fig. 1
alcama	zn-5	s854Tg	standard conditions	Protruding-mouth	pancreas	IHC	Fig. 1
alcama	zn-5	s854Tg	standard conditions	Long-pec	pancreas	IHC	Fig. 1
alcama	zn-5	WT	standard conditions	Protruding-mouth	liver	IHC	Fig. 6
alcama	zn-5	WT	standard conditions	Protruding-mouth	pancreas	IHC	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-foxa2	standard conditions	Long-pec	pancreas decreased size, abnormal	Fig. 7
WT + MO1-foxa2	standard conditions	Long-pec	pancreas development disrupted, abnormal	Fig. 7
WT + MO1-her5	standard conditions	Prim-15	endodermal cell fate specification disrupted, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Prim-15	liver decreased size, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Prim-15	pancreas decreased size, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Protruding-mouth	hepatic duct morphology, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Protruding-mouth	liver development disrupted, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Protruding-mouth	liver morphology, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Protruding-mouth	pancreas development disrupted, abnormal	Fig. 6
WT + MO1-her5	standard conditions	Protruding-mouth	pancreas morphology, abnormal	Fig. 6

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Shin et al., 2008 ZDB-PUB-080414-12 PMID:18394596

Multiple roles for Med12 in vertebrate endoderm development

Shin et al., 2008

ZDB-PUB-080414-12
PMID:18394596