Another key role for the cardiac neural crest in heart development.
Another key role for the cardiac neural crest in heart development.
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心脏神经嵴在心脏发育中的另一个关键作用。
DOI：
10.1152/ajpheart.01218.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Finnell,RichardH
中科院分区：
文献类型：
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作者：
Rosenquist,ThomasH;Finnell,RichardH
今年是两篇论文发表113周年，这两篇论文的关系最初并不明显：一篇是关于神经嵴细胞从神经外胚层迁移并呈现出多种表型的观察（11），另一篇是关于心脏起搏器/传导系统的初步描述(6)。随着技术的进步，这两种观测结果都以对数方式扩展，积累的数据显示出它们在发展和功能上的非凡重要性。神经外胚层细胞对面神经间充质形成的贡献（11）使胚层发育理论的原教旨主义信徒感到困惑，下一个世纪的研究表明，神经嵴的发育潜力更加多样化。神经嵴细胞可分化为其他几种间充质细胞类型，并可分化为黑素细胞、神经元和胶质细胞以及各种高度特化的内分泌和副内分泌细胞。这种显著的可塑性已经被Le Douarin等人（10），Sauka-Spengler和Bronner-Fraser(13)，以及Vickaryous和Hall（16）多次回顾，在他们提出的21世纪理论修订中，神经嵴成为第四胚层。Kirby等人(8)利用鸡胚胎心脏发育模型，进一步扩展了我们对神经嵴多重作用的理解，结果表明，来自颅神经嵴的间充质细胞是正常主动脉-肺分离所必需的，如果没有它们，心脏就会发育成流出道结构性缺陷。Conway等人(2)和其他人[由Hutson和Kirby(7)综述]进行了一系列实验，证实了心脏神经嵴在哺乳动物心脏发育中的作用。事实上，在Kirby等人(8)的开创性发现之后，神经嵴损伤在心脏缺陷形成中的潜在重要性很快被推断到人类身上[例如，Lammer等人(9)]，并且给予脊椎动物四腔心脏的头侧神经嵴区域现在得到了很好的认识，以至于被命名为“心脏神经嵴”[由Hutson和Kirby(7)以及Stoller和Epstein（15）评述]。心脏神经嵴源性心脏缺陷是一个独特的，公认的，并且在病因学上对儿科心脏病学家有用的类别。进一步的实验表明，心脏神经嵴对心脏发育的重要性超越了其变色龙一样的能力，即承担不同的细胞表型。Hutson和Kirby(7)讨论了其在心血管发育中的“间接参与”，Stoller和Epstein（15）引用了心脏神经嵴在复杂的诱导相互作用中对心脏发育至关重要。在目前的背景下，特别重要的是心脏神经嵴的诱导影响与心脏起搏/传导系统的发展的收敛。Gourdie和他的同事[例如，Cheng et al.(1)和Gourdie et al.(3,4)]发现，起搏和传导系统既不是来自一群特化的祖细胞，也不是来自心脏神经嵴；然而，他们推断了心脏神经嵴对心肌细胞的诱导作用，这一效应在鸡胚胎模型（12）和小鼠胚胎模型（14）中都得到了实验证据的支持。最近，一个研究小组在心脏神经嵴和起搏/传导系统的发展方面都有杰出的成就，他们进行了一项技术上复杂的合作，这在本期《美国人》杂志上有报道
THIS YEAR IS THE 113TH ANNIVERSARY of two publications whose relationship was not obvious initially: the observation that neural crest cells migrate away from the neural ectoderm and assume a wide variety of phenotypes (11) and the initial description of what became known as the pacemaking/conduction system of the heart (6). Both of these observations have been expanded logarithmically by advancing technology, and the accumulated data have shown their extraordinary developmental and functional importance. The contribution of cells from the neural ectodermal to the formation of face mesenchyme (11) confounded fundamentalist believers in the germ layer theory of development, and the next century of research showed that the developmental potential of the neural crest was even more diverse. Neural crest cells contribute to several other mesenchymal cell types, and they may be directed to differentiate into melanocytes, neurons, and glia and into a variety of highly specialized endocrine and paraendocrine cells. This remarkable plasticity has been reviewed several times, eg, by Le Douarin et al.(10), Sauka-Spengler and Bronner-Fraser (13), and Vickaryous and Hall (16), in whose proposed 21st-century revision of the theory, neural crest becomes the fourth germ layer. In an important expansion of our understanding of the multiple roles of the neural crest, Kirby et al.(8) used the chicken embryo model of heart development to show that mesenchymal cells from the cranial neural crest were required for normal aorticopulmonary septation, and, in their absence, the heart developed with structural defects of the outflow tract. Conway et al.(2) and others [reviewed by Hutson and Kirby (7)] have carried out a number of experiments that confirmed the role of the cardiac neural crest in mammalian heart development. Indeed, following the seminal discovery by Kirby et al.(8), the potential importance of neural crest impairment in the formation of heart defects was quickly extrapolated to humans [eg, Lammer et al.(9)], and the region of the cephalic neural crest that gives vertebrates the four-chambered heart now is so well appreciated that it has been named the “cardiac neural crest”[reviewed by Hutson and Kirby (7) and Stoller and Epstein (15)]. Cardiac neural crest-derived heart defects are a distinct, well-recognized, and etiologically useful category for pediatric cardiologists. Further experiments have demonstrated that the importance of the cardiac neural crest to heart development transcends its chameleon-like ability to assume diverse cellular phenotypes. Hutson and Kirby (7) discuss its “indirect participation” in cardiovascular development, and Stoller and Epstein (15) cite the cardiac neural crest in complex inductive interactions that are vital to heart development. Of particular significance in the present context is the convergence of the inductive influence of the cardiac neural crest with the development of the cardiac pacemaking/conduction system. Gourdie and his colleagues [eg, Cheng et al.(1) and Gourdie et al.(3, 4)] found that the pacemaking and conduction system was neither derived from a pool of specialized progenitor cells nor derived from the cardiac neural crest; however, they had inferred an inductive effect of the cardiac neural crest on myocardial cells, an effect supported by experimental evidence in both the chicken embryo model (12) and the mouse embryo model (14). Recently, a research team with outstanding credentials in the development of both the cardiac neural crest and the pacemaking/conduction system carried out a technically sophisticated collaboration that is reported in this issue of the American