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