PUBLICATION

Hhex regulates the specification and growth of the hepatopancreatic ductal system

Authors

Villasenor, A., Gauvrit, S., Collins, M.M., Maischein, H.M., Stainier, D.Y.R.

ID

ZDB-PUB-191108-32

Date

2019

Source

Developmental Biology 458(2): 228-236 (Journal)

Registered Authors

Maischein, Hans-Martin, Stainier, Didier

Keywords

Endoderm, Extrahepatic duct, Hepatopancreatic ductal system, Hhex, Yolk syncytial layer

MeSH Terms

Embryo, Nonmammalian/metabolism
Zebrafish/genetics
Zebrafish/metabolism
Animals, Genetically Modified/metabolism
Repressor Proteins/genetics
Repressor Proteins/metabolism*
Gene Expression Regulation, Developmental/genetics
Endothelial Cells/metabolism
Animals
Homeodomain Proteins/genetics
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Digestive System/metabolism
Endoderm/metabolism
Body Patterning/physiology
Hepatopancreas/embryology*
Hepatopancreas/growth & development*
Hepatopancreas/metabolism

(all 18)

PubMed

31697936 Full text @ Dev. Biol.

Abstract

Significant efforts have advanced our understanding of foregut-derived organ development; however, little is known about the molecular mechanisms that underlie the formation of the hepatopancreatic ductal (HPD) system. Here, we report a role for the homeodomain transcription factor Hhex in directing HPD progenitor specification in zebrafish. Loss of Hhex function results in impaired HPD system formation. We found that Hhex specifies a distinct population of HPD progenitors that gives rise to the cystic duct, common bile duct, and extra-pancreatic duct. Since hhex is not uniquely expressed in the HPD region but is also expressed in endothelial cells and the yolk syncytial layer (YSL), we tested the role of blood vessels as well as the YSL in HPD formation. We found that blood vessels are required for HPD patterning, but not for HPD progenitor specification. In addition, we found that Hhex is required in both the endoderm and the YSL for HPD development. Our results shed light on the mechanisms directing endodermal progenitors towards the HPD fate and emphasize the tissue specific requirement of Hhex during development.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
hhex	WT	standard conditions	Prim-5	blood vessel endothelial cell	ISH	Fig. 2
hhex	WT	standard conditions	20-25 somites	blood vessel endothelial cell	ISH	Fig. 2
hhex	WT	standard conditions	Protruding-mouth	common bile duct	ISH	Fig. 2
hhex	WT	standard conditions	Protruding-mouth	cystic duct	ISH	Fig. 2
hhex	WT	standard conditions	Prim-15	digestive system duct	ISH	Fig. 2
hhex	WT	standard conditions	Long-pec	digestive system duct	ISH	Fig. 2
hhex	WT	standard conditions	Prim-5	endoderm	ISH	Fig. 2
hhex	WT	standard conditions	20-25 somites	endoderm	ISH	Fig. 2
hhex	WT	standard conditions	Prim-15	endoderm	ISH	Fig. 2
hhex	WT	standard conditions	Protruding-mouth	extrahepatic duct	ISH	Fig. 2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
hhex^s721/s721	standard conditions	Prim-15	intestinal bulb primordium ptf1a expression absent, abnormal	Fig. 1
hhex^s721/s721	standard conditions	Prim-25	anterior pancreatic bud prox1a expression decreased amount, abnormal	Fig. 3
hhex^s721/s721	standard conditions	Prim-25	anterior pancreatic bud sox9b expression absent, abnormal	Fig. 3
hhex^s721/s721	standard conditions	Prim-25	digestive system duct prox1a expression decreased amount, abnormal	Fig. 3
hhex^s721/s721	standard conditions	Prim-25	digestive system duct sox9b expression absent, abnormal	Fig. 3
hhex^s721/s721	standard conditions	Prim-25	liver prox1a expression decreased amount, abnormal	Fig. 3
hhex^s721/s721	standard conditions	Prim-25	liver sox9b expression absent, abnormal	Fig. 3
hhex^s721/s721	standard conditions	Long-pec	digestive system duct ab-2f11 labeling absent, abnormal	Fig. 2
hhex^s721/s721	standard conditions	Long-pec	digestive system duct absent, abnormal	Fig. 2
hhex^s721/s721	standard conditions	Long-pec	extrapancreatic duct ab-2f11 labeling decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
as3Tg	Tg(-2.8fabp10a:EGFP)	Transgenic Insertion
gz19Tg	Tg(sst2:RFP)	Transgenic Insertion
jh1Tg	Tg(ptf1a:EGFP)	Transgenic Insertion
nim5Tg	TgBAC(prox1a:KALTA4,4xUAS-E1B:TagRFP)	Transgenic Insertion
s5		Point Mutation	npas4l
s721		Insertion	hhex
s722		Small Deletion	hhex
s854Tg	Tg(Xla.Eef1a1:GFP)	Transgenic Insertion
s870Tg	Tg(sox17:GFP)	Transgenic Insertion

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
hhex	MO1-hhex	MRPHLNO

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP
KALTA4	EFG	KALTA4
RFP	EFG	RFP
TagRFP	EFG	TagRFP

Mapping

Villasenor et al., 2019 ZDB-PUB-191108-32 PMID:31697936

Hhex regulates the specification and growth of the hepatopancreatic ductal system

Villasenor et al., 2019

ZDB-PUB-191108-32
PMID:31697936