Document Detail

Trk C receptor signaling regulates cardiac myocyte proliferation during early heart development in vivo.
MedLine Citation:
PMID:  11023679     Owner:  NLM     Status:  MEDLINE    
Neurotrophin-3 (NT-3) is a member of the neurotrophin family of growth factors, best characterized by its survival- and differentiation-inducing effects on developing neurons bearing the trk C receptor tyrosine kinase. Through analysis of NT-3 and trk C gene-targeted mice we have identified NT-3 as critically regulating cardiac septation, valvulogenesis, and conotruncal formation. Although these defects could reflect cardiac neural crest dysfunction, the expression of NT-3 and trk C by cardiac myocytes prior to neural crest migration prompted analysis of cell-autonomous actions of NT-3 on cardiac myocytes. Retroviral-mediated overexpression of truncated trk C receptor lacking kinase activity was used to inhibit activation of trk C by endogenous NT-3, during early heart development in ovo. During the first week of chicken development, expression of truncated trk C reduced myocyte clone size by more than 60% of control clones. Direct mitogenic actions of NT-3 on embryonic cardiac myocytes were demonstrated by analysis of BrdU incorporation or PCNA immunoreactivity in control and truncated trk C-expressing clones. Inhibition of trk C signaling reduced cardiac myocyte proliferation during the first week of development, but had no effect at later times. These studies demonstrate that endogenous NT-3:trk C signaling regulates cardiac myocyte proliferation during cardiac looping and the establishment of ventricular trabeculation but that myocyte proliferation becomes NT-3 independent during the second week of embryogenesis.
M I Lin; I Das; G M Schwartz; P Tsoulfas; T Mikawa; B L Hempstead
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Developmental biology     Volume:  226     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-08     Completed Date:  2000-11-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  180-91     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
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MeSH Terms
Amino Acid Sequence
Autocrine Communication
Cell Division / drug effects
Chick Embryo
DNA Replication / drug effects
DNA, Complementary / genetics
Defective Viruses / genetics
Fetal Heart / cytology*,  drug effects
Fibroblast Growth Factor 1
Fibroblast Growth Factor 2 / physiology
Genetic Vectors / genetics
Molecular Sequence Data
Myocardium / cytology*,  metabolism
Neurotrophin 3 / physiology*
Peptide Fragments / genetics,  physiology
Proliferating Cell Nuclear Antigen / analysis
Receptor, trkC / chemistry,  deficiency,  drug effects,  genetics,  physiology*
Recombinant Fusion Proteins / chemistry,  physiology
Retroviridae / genetics
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/Neurotrophin 3; 0/Peptide Fragments; 0/Proliferating Cell Nuclear Antigen; 0/Recombinant Fusion Proteins; 103107-01-3/Fibroblast Growth Factor 2; 104781-85-3/Fibroblast Growth Factor 1; EC, trkC

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