Cardiac Malformations in Pdgfr alpha Mutant Embryos Are Associated With Increased Expression of WT1 and Nkx2.5 in the Second Heart Field

Author(s):
Bax, N.A.M.; Bleyl, S.B.; Gallini, R.; Wisse, L.J.; Hunter, J.; Oorschot, A.A.M. van; Mahtab, E.A.F.; Lie-Venema, H.; Goumans, M.J.; Betsholtz, C.; Gittenberger-de Groot, A.C.
Published
2010
Publication type
Article / Letter to editor

Abstract

Platelet-derived growth factor receptor alpha (Pdgfr alpha) identifies cardiac progenitor cells in the posterior part of the second heart field. We aim to elucidate the role of Pdgfra in this region. Hearts of Pdgfr alpha-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 Pdgfra 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 alpha 4-integrin expression. Our data provide novel insight for a possible role for Pdgfra 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. (C) 2010 Wiley-Liss, Inc.

Pdgfr alpha knockout mouse embryos heart development dorsal mesenchymal protrusion (DMP) sinus venosus myocardium epicardium-derived cells (EPDCs) vascular smooth-muscle growth-factor receptor-alpha avian heart epicardial development coronary-artery cell-migration deficient mice patch mouse venous pole
Date issued
2010-08-31
Language
English
Is part of
Developmental Dynamics (2010), Vol. 239, no. 8, p. 2307-2317
hdl
1887/109626
doi
10.1002/dvdy.22363