PUBLICATION

Intra-endodermal interactions are required for pancreatic beta cell induction

Authors

Chung, W.S., and Stainier, D.Y.

ID

ZDB-PUB-080421-3

Date

2008

Source

Developmental Cell 14(4): 582-593 (Journal)

Registered Authors

Chung, Won-Suk, Stainier, Didier

Keywords

DEVBIO

MeSH Terms

Mesoderm/cytology
Mesoderm/physiology
Insulin-Secreting Cells/cytology
Insulin-Secreting Cells/physiology*
Signal Transduction/physiology*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Receptors, G-Protein-Coupled/genetics
Receptors, G-Protein-Coupled/metabolism
Embryonic Induction/physiology*
Cell Lineage
Hedgehog Proteins/genetics
Hedgehog Proteins/metabolism
Recombinant Fusion Proteins/genetics
Recombinant Fusion Proteins/metabolism
Animals, Genetically Modified
Zebrafish*/anatomy & histology
Zebrafish*/embryology
Transgenes
Cell Transplantation
Cell Differentiation/physiology*
Animals
Endoderm/cytology
Endoderm/physiology*

(all 24)

PubMed

18410733 Full text @ Dev. Cell

Abstract

The cellular origin of signals that regulate pancreatic beta cell induction is not clearly defined. Here, we investigate the seeming paradox that Hedgehog/Smoothened signaling functions during gastrulation to promote pancreatic beta cell development in zebrafish, yet has an inhibitory role during later stages of pancreas development in amniotes. Our cell transplantation experiments reveal that in zebrafish, Smoothened function is not required in beta cell precursors. At early somitogenesis stages, when the zebrafish endoderm first forms a sheet, pancreatic beta cell precursors lie closest to the midline; however, the requirement for Smoothened lies in their lateral neighbors, which ultimately give rise to the exocrine pancreas and intestine. Thus, pancreatic beta cell induction requires Smoothened function cell-nonautonomously during gastrulation, to allow subsequent intra-endodermal interactions. These results clarify the function of Hedgehog signaling in pancreas development, identify an unexpected cellular source of factors that regulate beta cell specification, and uncover complex patterning and signaling interactions within the endoderm.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
DsRed	noto^n1/n1; s903Tg; zf5Tg	standard conditions	14-19 somites		endoderm	IFL	Fig. 3
DsRed	s903Tg	standard conditions	1-4 somites		endoderm	IFL	Fig. 2
DsRed	s903Tg; zf5Tg	standard conditions	10-13 somites		endoderm	IFL	Fig. 1
DsRed	s903Tg; zf5Tg	standard conditions	14-19 somites		endoderm	IFL	Fig. 3
DsRed	s903Tg; zf5Tg	standard conditions	14-19 somites		endoderm	IFL	Fig. 1
DsRed	s903Tg; zf5Tg	standard conditions	14-19 somites		endodermal cell	IFL	Fig. S6
DsRed	s903Tg; zf5Tg + MO3-sox32	standard conditions	14-19 somites		endodermal cell	IFL	Fig. S6
DsRed	smo^{hi1640Tg/hi1640Tg}; s903Tg	standard conditions	1-4 somites		endoderm	IFL	Fig. 2
GFP	noto^n1/n1; s903Tg; zf5Tg	standard conditions	14-19 somites	Not Detected	whole organism	IFL	Fig. 3
GFP	noto^n1/n1; zf5Tg	standard conditions	Long-pec		endocrine cell	IFL	Fig. 3

1 - 10 of 54

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
noto^n1/n1; zf5Tg	standard conditions	Long-pec	pancreas development disrupted, abnormal	Fig. 3
noto^n1/n1; zf5Tg	standard conditions	Long-pec	pancreas endocrine cell decreased amount, abnormal	Fig. 3
noto^n1/n1; zf5Tg	standard conditions	Pec-fin	pancreas development disrupted, abnormal	Fig. 3
noto^n1/n1; zf5Tg	standard conditions	Pec-fin	pancreas endocrine cell decreased amount, abnormal	Fig. 3
smo^{hi1640Tg/hi1640Tg}	standard conditions	Prim-5	pancreas development disrupted, abnormal	Fig. S1
smo^{hi1640Tg/hi1640Tg}	standard conditions	Prim-25	pancreas development disrupted, abnormal	Fig. S1
smo^{hi1640Tg/hi1640Tg}	standard conditions	Long-pec	pancreas development disrupted, abnormal	Fig. S1
smo^{hi1640Tg/hi1640Tg}; zf5Tg	standard conditions	Day 4	liver development disrupted, abnormal	Fig. 2
smo^{hi1640Tg/hi1640Tg}; zf5Tg	standard conditions	Day 4	liver morphology, abnormal	Fig. 2
smo^{hi1640Tg/hi1640Tg}; zf5Tg	standard conditions	Day 4	pancreas development disrupted, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hi1640Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	smo
n1		Small Deletion	noto
s854Tg	Tg(Xla.Eef1a1:GFP)	Transgenic Insertion
s870Tg	Tg(sox17:GFP)	Transgenic Insertion
s903Tg	Tg(sox17:DsRed)	Transgenic Insertion
zf5Tg	Tg(-4.0ins:GFP)	Transgenic Insertion

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
sox32	MO3-sox32	MRPHLNO

Fish

Fish
noto^n1/n1; s903Tg; zf5Tg
noto^n1/n1; zf5Tg
s854Tg
s870Tg
s903Tg
s903Tg; zf5Tg
s903Tg; zf5Tg + MO3-sox32
smo^{hi1640Tg/hi1640Tg}
smo^{hi1640Tg/hi1640Tg}; s854Tg
smo^{hi1640Tg/hi1640Tg}; s903Tg

1 - 10 of 13

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
GFP	EFG	GFP

Mapping

Chung et al., 2008 ZDB-PUB-080421-3 PMID:18410733

Intra-endodermal interactions are required for pancreatic beta cell induction

Chung et al., 2008

ZDB-PUB-080421-3
PMID:18410733