PMID- 10476967
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20171116
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 400
IP  - 6747
DP  - 1999 Aug 26
TI  - Notch signalling controls pancreatic cell differentiation.
PG  - 877-81
AB  - The pancreas contains both exocrine and endocrine cells, but the molecular
      mechanisms controlling the differentiation of these cell types are largely
      unknown. Despite their endodermal origin, pancreatic endocrine cells share
      several molecular characteristics with neurons, and, like neurons in the central 
      nervous system, differentiating endocrine cells in the pancreas appear in a
      scattered fashion within a field of progenitor cells. This indicates that they
      may be generated by lateral specification through Notch signalling. Here, to test
      this idea, we analysed pancreas development in mice genetically altered at
      several steps in the Notch signalling pathway. Mice deficient for Delta-like gene
      1 (Dll1) or the intracellular mediator RBP-Jkappa showed accelerated
      differentiation of pancreatic endocrine cells. A similar phenotype was observed
      in mice over-expressing neurogenin 3 (ngn 3) or the intracellular form of Notch3 
      (a repressor of Notch signalling). These data provide evidence that ngn3 acts as 
      proendocrine gene and that Notch signalling is critical for the decision between 
      the endocrine and progenitor/exocrine fates in the developing pancreas.
FAU - Apelqvist, A
AU  - Apelqvist A
AD  - Department of Microbiology, University of Umea, Sweden.
FAU - Li, H
AU  - Li H
FAU - Sommer, L
AU  - Sommer L
FAU - Beatus, P
AU  - Beatus P
FAU - Anderson, D J
AU  - Anderson DJ
FAU - Honjo, T
AU  - Honjo T
FAU - Hrabe de Angelis, M
AU  - Hrabe de Angelis M
FAU - Lendahl, U
AU  - Lendahl U
FAU - Edlund, H
AU  - Edlund H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Notch3 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Rbpj protein, mouse)
RN  - 0 (Receptor, Notch3)
RN  - 0 (Receptor, Notch4)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Notch)
RN  - 0 (Xenopus Proteins)
RN  - 0 (delta protein)
RN  - 0 (neurogenin, Xenopus)
RN  - 146991-60-8 (Notch4 protein, mouse)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Cell Differentiation/physiology
MH  - DNA-Binding Proteins/metabolism
MH  - Immunoglobulin J Recombination Signal Sequence-Binding Protein
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Proteins/metabolism/*physiology
MH  - Mice
MH  - Mice, Transgenic
MH  - Nerve Tissue Proteins/metabolism
MH  - *Nuclear Proteins
MH  - Pancreas/*cytology/*embryology
MH  - Proto-Oncogene Proteins/metabolism
MH  - Receptor, Notch3
MH  - Receptor, Notch4
MH  - *Receptors, Cell Surface
MH  - Receptors, Notch
MH  - Signal Transduction
MH  - *Xenopus Proteins
EDAT- 1999/09/07 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/09/07 09:00
PHST- 1999/09/07 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/09/07 09:00 [entrez]
AID - 10.1038/23716 [doi]
PST - ppublish
SO  - Nature. 1999 Aug 26;400(6747):877-81. doi: 10.1038/23716.