Cooperation between the PDGF receptors in cardiac neural crest cell migration.
Neural crest cells (NCCs) are essential components of the sympathetic nervous system, skin, craniofacial skeleton, and aortic arch. It has been known for many years that perturbation of migration, proliferation, and/or differentiation of these cells leads to birth defects such as cleft palate and persistent truncus arteriosus (PTA). Previously, we had shown that disruption of the platelet-derived growth factor receptor (PDGFR) alpha in NCCs resulted in defects in craniofacial and aortic arch development, the latter with variable penetrance. Because we observed ventricular septal defects in embryos that are null for the PDGFRbeta, we hypothesized that both PDGF receptors are involved in NCC formation. Here, we show that both receptors are expressed in cardiac NCCs and that the combined loss of the PDGFRalpha and PDGFRbeta in NCCs resulted in NCC-related heart abnormalities, including PTA and a ventricular septal defect (VSD). Using NCC lineage tracing, we observed that loss of PDGF receptor signaling resulted in reduced NCCs in the conotruncus region, leading to defects in aortic arch septation. These results indicate that while PDGFRalpha plays a predominant role in NCC development, the PDGFRbeta is expressed by and functions in cardiac NCCs. Combined PDGF receptor signaling is required for sufficient recruitment of cardiac NCCs into the conotruncal region and for formation of the aortico-pulmonary and ventricular septum.
Richarte
Alicia M
AM
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Mead
Holly B
HB
Tallquist
Michelle D
MD
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology*; D010641:Phenotype; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism / Q000502:physiology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor