PUBLICATION

TALE-Family homeodomain proteins regulate endodermal sonic hedgehog expression and pattern the anterior endoderm

Authors

diIorio, P., Alexa, K., Choe, S.K., Etheridge, L., and Sagerström, C.G.

ID

ZDB-PUB-070212-42

Date

2007

Source

Developmental Biology 304(1): 221-231 (Journal)

Registered Authors

Choe, Seong-Kyu, diIorio, Philip, Etheridge, Letitiah, Sagerström, Charles

Keywords

Homeodomain transcription factor, Endoderm patterning, Pancreas development: hedgehog signaling, foxa2, meis, pbx, lazarus, sox32

MeSH Terms

Animals
Body Patterning/physiology*
DNA-Binding Proteins/metabolism*
Digestive System/embryology*
Endoderm/metabolism*
Gene Expression Regulation, Developmental*
Hedgehog Proteins/metabolism*
Homeodomain Proteins/metabolism*
In Situ Hybridization
Insulin/metabolism
Oligonucleotides
Xenopus Proteins/metabolism*
Zebrafish/embryology*
Zebrafish Proteins/metabolism*

(all 14)

PubMed

17289013 Full text @ Dev. Biol.

Abstract

sonic hedgehog (shh) is expressed in anterior endoderm, where it is required to repress pancreas gene expression and to pattern the endoderm, but the pathway controlling endodermal shh expression is unclear. We find that expression of meis3, a TALE class homeodomain gene, coincides with shh expression in the endoderm of zebrafish embryos. Using a dominant negative construct or anti-sense morpholino oligos (MOs) to disrupt meis3 function, we observe ectopic insulin expression in anterior endoderm. This phenotype is also observed when meis3 MOs are targeted to the endoderm, suggesting that meis3 acts within the endoderm to restrict insulin expression. We also find that meis3 is required for endodermal shh expression, indicating that meis3 acts upstream of shh to restrict insulin expression. Loss of pbx4, a TALE gene encoding a Meis cofactor, produces the same phenotype as loss of meis3, consistent with Meis3 acting in a complex with Pbx4 as reported in other systems. Lastly, we observe a progressive anterior displacement of endoderm-derived organs upon disruption of meis3 or pbx4, apparently as a result of underdevelopment of the pharyngeal region. Our data indicate that meis3 and pbx4 regulate shh expression in anterior endoderm, thereby influencing patterning and growth of the foregut.

Genes / Markers

Marker	Marker Type	Name
cpa5	GENE	carboxypeptidase A5
dlx2a	GENE	distal-less homeobox 2a
foxa2	GENE	forkhead box A2
hoxb6a	GENE	homeobox B6a
hoxb6b	GENE	homeobox B6b
ins	GENE	preproinsulin
meis1b	GENE	Meis homeobox 1 b
meis3	GENE	myeloid ecotropic viral integration site 3
pbx4	GENE	pre-B-cell leukemia transcription factor 4
pdx1	GENE	pancreatic and duodenal homeobox 1

1 - 10 of 13

Show

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: pharmaceutical	Prim-5	endocrine pancreas mislocalised anteriorly, abnormal	Fig. 2
WT	chemical treatment: pharmaceutical	Long-pec	endocrine pancreas mislocalised anteriorly, abnormal	Fig. 2
WT	chemical treatment: pharmaceutical	Long-pec	pharyngeal arch 3-7 hypoplastic, abnormal	Fig. 6
WT	chemical treatment: pharmaceutical	Protruding-mouth	exocrine pancreas mislocalised anteriorly, abnormal	Fig. 6
WT	chemical treatment: pharmaceutical	Protruding-mouth	liver aplastic, abnormal	Fig. 6
WT	chemical treatment: pharmaceutical	Protruding-mouth	liver mislocalised anteriorly, abnormal	Fig. 6
WT + MO1-meis3	chemical treatment: pharmaceutical	Prim-5	endocrine pancreas mislocalised anteriorly, abnormal	Fig. 2
WT + MO1-meis3	chemical treatment: pharmaceutical	Protruding-mouth	endocrine pancreas mislocalised anteriorly, abnormal	Fig. 5
WT + MO1-meis3	standard conditions	Protruding-mouth	endocrine pancreas mislocalised anteriorly, abnormal	Fig. 5
WT + MO2-meis3	standard conditions	Protruding-mouth	endocrine pancreas mislocalised anteriorly, abnormal	Fig. 5

1 - 10 of 19

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b557		Point Mutation	pbx4
s854Tg	Tg(Xla.Eef1a1:GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
meis3	MO1-meis3	MRPHLNO
meis3	MO2-meis3	MRPHLNO

Fish

Fish
pbx4^b557/b557
WT
WT + MO1-meis3
WT + MO2-meis3

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

diIorio et al., 2007 ZDB-PUB-070212-42 PMID:17289013

TALE-Family homeodomain proteins regulate endodermal sonic hedgehog expression and pattern the anterior endoderm

diIorio et al., 2007

ZDB-PUB-070212-42
PMID:17289013