Document Detail

Development of adrenal chromaffin cells is largely normal in mice lacking the receptor tyrosine kinase c-Ret.
MedLine Citation:
PMID:  12591599     Owner:  NLM     Status:  MEDLINE    
c-Ret encodes a receptor tyrosine kinase that is essential for normal development of the kidney as well as enteric and sympathetic neurons. Since sympathetic neurons and neuroendocrine chromaffin cells originate from a common progenitor cell, we have examined the relevance of c-Ret for the development of adrenal chromaffin cells by analyzing mouse mutants lacking c-Ret. Adrenal chromaffin cells express c-Ret mRNA at embryonic day (E) 12.5 and 13.5, yet levels of expression decline at later embryonic and postnatal ages. Adrenal medullae of c-Ret deficient mice show normal numbers of tyrosine hydroxylase (TH)-immunoreactive cells at E13.5 and at birth. Ultrastructurally, adrenal chromaffin cells of c-Ret(-/-) mice appear unaltered: chromaffin cells develop typical secretory chromaffin granules, the morphological hallmark of chromaffin cells, and synaptic terminals appear normal. However, adrenaline levels and numbers of chromaffin cells immunoreactive for the adrenaline synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) are reduced by about 30% in c-Ret-deficient mice arguing for a direct or indirect role of c-Ret in the regulation of PNMT. Thus, despite expression of c-Ret, adrenal chromaffin cells develop largely normal in mice lacking c-Ret. We therefore conclude that sympathetic neurons and neuroendocrine chromaffin cells profoundly differ in their requirement for c-Ret signaling during development.
Alexandra Allmendinger; Elvira Stoeckel; Mart Saarma; Klaus Unsicker; Katrin Huber
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Mechanisms of development     Volume:  120     ISSN:  0925-4773     ISO Abbreviation:  Mech. Dev.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-19     Completed Date:  2003-10-23     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9101218     Medline TA:  Mech Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  299-304     Citation Subset:  IM    
Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.
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MeSH Terms
Adrenal Glands / cytology*,  embryology,  growth & development*,  ultrastructure
Animals, Newborn
Cell Count
Cell Movement / genetics
Cell Survival / genetics
Chromaffin Cells / physiology*,  ultrastructure
Epinephrine / metabolism
Ganglia, Sympathetic / cytology,  growth & development
Gene Expression Regulation, Developmental
Mice, Knockout
Norepinephrine / metabolism
Phenylethanolamine N-Methyltransferase / metabolism
Proto-Oncogene Proteins / deficiency,  genetics*,  metabolism
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases / deficiency,  genetics*,  metabolism
Reference Values
Signal Transduction
Tyrosine 3-Monooxygenase / metabolism
Reg. No./Substance:
0/Proto-Oncogene Proteins; 51-41-2/Norepinephrine; 51-43-4/Epinephrine; EC 3-Monooxygenase; EC N-Methyltransferase; EC Proteins c-ret; EC Protein-Tyrosine Kinases; EC protein, mouse

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