Document Detail


The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells.
MedLine Citation:
PMID:  19665969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed alpha cells fail to correct the hypoglucagonemia since they subsequently acquire a beta cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.
Authors:
Patrick Collombat; Xiaobo Xu; Philippe Ravassard; Beatriz Sosa-Pineda; Sébastien Dussaud; Nils Billestrup; Ole D Madsen; Palle Serup; Harry Heimberg; Ahmed Mansouri
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  138     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-08-31     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  449-62     Citation Subset:  IM    
Affiliation:
Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg, D-37077 Göttingen, Germany. collombat@unice.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Basic Helix-Loop-Helix Transcription Factors / metabolism
Cell Differentiation*
Diabetes Mellitus, Experimental / metabolism
Glucagon / deficiency
Glucagon-Secreting Cells / cytology*
Homeodomain Proteins / metabolism*
Insulin-Secreting Cells / cytology*
Islets of Langerhans / cytology
Mice
Nerve Tissue Proteins / metabolism
Paired Box Transcription Factors / metabolism*
Pancreas / cytology*,  growth & development
Stem Cells / cytology*
Grant Support
ID/Acronym/Agency:
R01 DK060542-07/DK/NIDDK NIH HHS; U19 DK 072495-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Homeodomain Proteins; 0/Nerve Tissue Proteins; 0/Neurog3 protein, mouse; 0/Paired Box Transcription Factors; 0/Pax4 protein, mouse; 9007-92-5/Glucagon
Comments/Corrections
Comment In:
Cell. 2009 Aug 7;138(3):424-6   [PMID:  19665963 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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