Cooperation between the PDGF receptors in cardiac neural crest cell migration
Cooperation between the PDGF receptors in cardiac neural crest cell migration
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DOI：
10.1016/j.ydbio.2007.04.023
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发表时间：
2007-06-15
影响因子：
2.7
通讯作者：
Tallquist, Michelle D.
中科院分区：
文献类型：
--
作者：
Richarte, Alicia M.;Mead, Holly B.;Tallquist, Michelle D.
神经嵴细胞（neural crest cells，NCC）是交感神经系统、皮肤、颅面骨骼和主动脉弓的重要组成部分，其迁移、增殖和/或分化受到干扰可导致腭裂和永存动脉干（persistent truncus arteriosus，PTA）等出生缺陷。以前，我们已经证明，在NCC中血小板衍生生长因子受体（PDGFR）α的破坏导致颅面和主动脉弓发育的缺陷，后者具有可变的收缩率。因为我们观察到胚胎中的室间隔缺损没有PDGFR，我们假设两种PDGF受体都参与了NCC的形成。在这里，我们发现这两种受体在心脏NCC中表达，并且NCC中PDGFR α和PDGFR β的联合缺失导致了NCC相关的心脏异常，包括PTA和室间隔缺损（VSD）。使用NCC谱系追踪，我们观察到PDGF受体信号传导的丧失导致圆锥干区域的NCC减少，导致主动脉弓分隔缺陷。这些结果表明，虽然PDGFR α在NCC的发展中起主要作用，但PDGFR在心脏NCC中表达并发挥作用。联合的PDGF受体信号传导是心脏NCC充分募集到圆锥动脉干区域以及肺动脉和心室间隔形成所必需的。(c)2007年爱思唯尔公司All rights reserved.
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 PDGFR, 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 PDGFR alpha and PDGFR beta 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 PDGFR alpha plays a predominant role in NCC development, the PDGFR 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. (c) 2007 Elsevier Inc. All rights reserved.