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Cardiac malformations in Pdgfrα mutant embryos are associated with increased expression of WT1 and Nkx2.5 in the second heart field
Author(s) -
Bax Noortje A.M.,
Bleyl Steven B.,
Gallini Radiosa,
Wisse Lambertus J.,
Hunter Jennifer,
Van Oorschot Angelique A.M.,
Mahtab Edris A.F.,
LieVenema Heleen,
Goumans MarieJose,
Betsholtz Christer,
Gittenbergerde Groot Adriana C.
Publication year - 2010
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.22363
Subject(s) - sinus venosus , biology , heart development , platelet derived growth factor receptor , medicine , endocrinology , anatomy , receptor , growth factor , embryonic stem cell , gene , biochemistry
Platelet‐derived growth factor receptor alpha ( Pdgfr α) identifies cardiac progenitor cells in the posterior part of the second heart field. We aim to elucidate the role of Pdgfr α in this region. Hearts of Pdgfr α‐deficient mouse embryos (E9.5–E14.5) showed cardiac malformations consisting of atrial and sinus venosus myocardium hypoplasia, including venous valves and sinoatrial node. In vivo staining for Nkx2.5 showed increased myocardial expression in Pdgfr α mutants, confirmed by Western blot analysis. Due to hypoplasia of the primary atrial septum, mesenchymal cap, and dorsal mesenchymal protrusion, the atrioventricular septal complex failed to fuse. Impaired epicardial development and severe blebbing coincided with diminished migration of epicardium‐derived cells and myocardial thinning, which could be linked to increased WT1 and altered α4‐integrin expression. Our data provide novel insight for a possible role for Pdgfr α in transduction pathways that lead to repression of Nkx2.5 and WT1 during development of posterior heart field–derived cardiac structures. Developmental Dynamics 239:2307–2317, 2010. © 2010 Wiley‐Liss, Inc.