Document Detail


Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation.
MedLine Citation:
PMID:  21081123     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interactions between cells from the ectoderm and mesoderm influence development of the endodermally-derived pancreas. While much is known about how mesoderm regulates pancreatic development, relatively little is understood about how and when the ectodermally-derived neural crest regulates pancreatic development and specifically, beta cell maturation. A previous study demonstrated that signals from the neural crest regulate beta cell proliferation and ultimately, beta cell mass. Here, we expand on that work to describe timing of neural crest arrival at the developing pancreatic bud and extend our knowledge of the non-cell autonomous role for neural crest derivatives in the process of beta cell maturation. We demonstrated that murine neural crest entered the pancreatic mesenchyme between the 26 and 27 somite stages (approximately 10.0 dpc) and became intermingled with pancreatic progenitors as the epithelium branched into the surrounding mesenchyme. Using a neural crest-specific deletion of the Forkhead transcription factor Foxd3, we ablated neural crest cells that migrate to the pancreatic primordium. Consistent with previous data, in the absence of Foxd3, and therefore the absence of neural crest cells, proliferation of insulin-expressing cells and insulin-positive area are increased. Analysis of endocrine cell gene expression in the absence of neural crest demonstrated that, although the number of insulin-expressing cells was increased, beta cell maturation was significantly impaired. Decreased MafA and Pdx1 expression illustrated the defect in beta cell maturation; we discovered that without neural crest, there was a reduction in the percentage of insulin-positive cells that co-expressed Glut2 and Pdx1 compared to controls. In addition, transmission electron microscopy analyses revealed decreased numbers of characteristic insulin granules and the presence of abnormal granules in insulin-expressing cells from mutant embryos. Together, these data demonstrate that the neural crest is a critical regulator of beta cell development on two levels: by negatively regulating beta cell proliferation and by promoting beta cell maturation.
Authors:
Jennifer L Plank; Nathan A Mundell; Audrey Y Frist; Alison W LeGrone; Thomas Kim; Melissa A Musser; Teagan J Walter; Patricia A Labosky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-23
Journal Detail:
Title:  Developmental biology     Volume:  349     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-02-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  321-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. jennifer.plank@vanderbilt.edu
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MeSH Terms
Descriptor/Qualifier:
Ablation Techniques
Age Factors
Animals
DNA Primers / genetics
Forkhead Transcription Factors / genetics
Gene Deletion
Gene Expression Regulation, Developmental / physiology*
Histological Techniques
Immunohistochemistry
Insulin-Secreting Cells / cytology*,  physiology,  ultrastructure
Mice
Microscopy, Electron, Transmission
Neural Crest / embryology*
Pancreas / cytology,  embryology*
Polymerase Chain Reaction
Signal Transduction / physiology*
Grant Support
ID/Acronym/Agency:
CA68485/CA/NCI NIH HHS; DK20593/DK/NIDDK NIH HHS; DK58404/DK/NIDDK NIH HHS; DK59637/DK/NIDDK NIH HHS; EY08126/EY/NEI NIH HHS; F31-NS065604/NS/NINDS NIH HHS; HD15052/HD/NICHD NIH HHS; P60-DK020593/DK/NIDDK NIH HHS; R01 HD036720-11/HD/NICHD NIH HHS; R01 HD036720-11S1/HD/NICHD NIH HHS; R01-HD036720/HD/NICHD NIH HHS; T32-DK07563/DK/NIDDK NIH HHS; T35-DK007383/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Forkhead Transcription Factors; 0/FoxO3 protein, mouse
Comments/Corrections

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