Document Detail

The novel transmembrane protein Tmem2 is essential for coordination of myocardial and endocardial morphogenesis.
MedLine Citation:
PMID:  21896630     Owner:  NLM     Status:  MEDLINE    
Coordination between adjacent tissues plays a crucial role during the morphogenesis of developing organs. In the embryonic heart, two tissues - the myocardium and the endocardium - are closely juxtaposed throughout their development. Myocardial and endocardial cells originate in neighboring regions of the lateral mesoderm, migrate medially in a synchronized fashion, collaborate to create concentric layers of the heart tube, and communicate during formation of the atrioventricular canal. Here, we identify a novel transmembrane protein, Tmem2, that has important functions during both myocardial and endocardial morphogenesis. We find that the zebrafish mutation frozen ventricle (frv) causes ectopic atrioventricular canal characteristics in the ventricular myocardium and endocardium, indicating a role of frv in the regional restriction of atrioventricular canal differentiation. Furthermore, in maternal-zygotic frv mutants, both myocardial and endocardial cells fail to move to the midline normally, indicating that frv facilitates cardiac fusion. Positional cloning reveals that the frv locus encodes Tmem2, a predicted type II single-pass transmembrane protein. Homologs of Tmem2 are present in all examined vertebrate genomes, but nothing is known about its molecular or cellular function in any context. By employing transgenes to drive tissue-specific expression of tmem2, we find that Tmem2 can function in the endocardium to repress atrioventricular differentiation within the ventricle. Additionally, Tmem2 can function in the myocardium to promote the medial movement of both myocardial and endocardial cells. Together, our data reveal that Tmem2 is an essential mediator of myocardium-endocardium coordination during cardiac morphogenesis.
Ronald Totong; Thomas Schell; Fabienne Lescroart; Lucile Ryckebüsch; Yi-Fan Lin; Tomasz Zygmunt; Lukas Herwig; Alice Krudewig; Dafna Gershoony; Heinz-Georg Belting; Markus Affolter; Jesús Torres-Vázquez; Deborah Yelon
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-07     Completed Date:  2011-11-22     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  4199-205     Citation Subset:  IM    
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MeSH Terms
Cloning, Molecular
Crosses, Genetic
Endocardium / metabolism*
Gene Expression Regulation, Developmental*
Heart / embryology*
In Situ Hybridization
Membrane Proteins / genetics,  physiology*
Microscopy, Fluorescence / methods
Models, Genetic
Myocardium / metabolism*
Tissue Distribution
Zebrafish Proteins / genetics,  physiology*
Grant Support
Reg. No./Substance:
0/Membrane Proteins; 0/Tmem2 protein, zebrafish; 0/Zebrafish Proteins

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

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