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Podoplanin deficient mice show a rhoa‐related hypoplasia of the sinus venosus myocardium including the sinoatrial node
Author(s) -
Mahtab Edris A.F.,
VicenteSteijn Rebecca,
Hahurij Nathan D.,
Jongbloed Monique R.M.,
Wisse Lambertus J.,
DeRuiter Marco C.,
Uhrin Pavel,
Zaujec Jan,
Binder Bernd R.,
Schalij Martin J.,
Poelmann Robert E.,
GittenbergerDe Groot Adriana C.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21819
Subject(s) - sinus venosus , podoplanin , sinoatrial node , biology , hypoplasia , anatomy , rhoa , vasa vasorum , mesoderm , pathology , medicine , immunohistochemistry , endocrinology , microbiology and biotechnology , embryonic stem cell , signal transduction , heart rate , biochemistry , gene , blood pressure
We investigated the role of podoplanin in development of the sinus venosus myocardium comprising the sinoatrial node, dorsal atrial wall, and primary atrial septum as well as the myocardium of the cardinal and pulmonary veins. We analyzed podoplanin wild‐type and knockout mouse embryos between embryonic day 9.5–15.5 using immunohistochemical marker podoplanin; sinoatrial‐node marker HCN4; myocardial markers MLC‐2a, Nkx2.5, as well as Cx43; coelomic marker WT‐1; and epithelial‐to‐mesenchymal transformation markers E‐cadherin and RhoA. Three‐dimensional reconstructions were made and myocardial morphometry was performed. Podoplanin mutants showed hypoplasia of the sinoatrial node, primary atrial septum, and dorsal atrial wall. Myocardium lining the wall of the cardinal and pulmonary veins was thin and perforated. Impaired myocardial formation is correlated with abnormal epithelial‐to‐mesenchymal transformation of the coelomic epithelium due to up‐regulated E‐cadherin and down‐regulated RhoA, which are controlled by podoplanin . Our results demonstrate an important role for podoplanin in development of sinus venosus myocardium. Developmental Dynamics 238:183–193, 2009. © 2008 Wiley‐Liss, Inc.