Development of the neural crest-derived intrinsic innervation of the human lung
Development of the neural crest-derived intrinsic innervation of the human lung
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DOI：
10.1165/rcmb.2007-0246oc
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发表时间：
2008-03-01
影响因子：
6.4
通讯作者：
Barlow, Amanda J.
中科院分区：
文献类型：
--
作者：
Burns, Alan J.;Thapar, Nikhil;Barlow, Amanda J.
与气道平滑肌（ASM）相关的神经组织的形成是正常肺发育和功能的特征。最近在动物模型中显示，内在神经元组织来源于神经嵴细胞（NCC）。由于NCC发育缺陷是一系列疾病状态（神经衰弱）的基础，因此确定人肺中NCC的时空发育非常重要，因为其发育缺陷可能具有病理生理学意义。本研究的目的是：（7）建立胚胎和胎儿肺内ASM和神经组织形成的时间过程，（2）研究肺内的内在神经组织是否来源于NCC，和（3）深入了解内在肺神经支配发展的可能信号机制。使用妊娠第6 - 12周的人肺组织，我们分析了ASM、NCC、神经元和神经胶质组织的形成，以及Gfr α 1（RET（转染期间重排）酪氨酸激酶信号通路的受体组分）的表达。我们的研究结果表明，NCC积累沿着分支气道，与ASM密切相关，并分化为神经元和胶质细胞。肺内的神经嵴源性神经组织强烈表达膜结合的GFR α 1，并且可溶性GFR α 1在肺间充质内表达，但仅在早期发育阶段。这些发现共同表明，人肺的内在神经支配来源于神经嵴。
The formation of neural tissue, in association with airway smooth muscle (ASM), is a feature of normal lung development and function. Intrinsic neuronal tissue has recently been shown, in animal models, to be derived from neural crest cells (NCC). Since defects in NCC development underlie a range of disease states (neurocristopathies), it is important to determine the spatiotemporal development of NCC in the human lung, as defects in their development could have pathophysiologic implications. The aims of this study were to: (7) establish a time course for the formation of ASM and neural tissue within the embryonic and fetal human lung, (2) investigate whether intrinsic neural tissue within the lung is derived from NCC, and (3) gain insight into the possible signaling mechanisms underlying the development of the intrinsic lung innervation. Using human lung tissue from Weeks 6 to 12 of gestation, we analyzed the formation of ASM, NCC, neuronal and glial tissue, and the expression of Gfr alpha 1, a receptor component of the RET (rearranged during transfection) tyrosine kinase signaling pathway. Our results showed that NCC accumulated along the branching airways, in close association with the ASM, and differentiated into neurons and glia. Neural crest-derived neural tissue within the lung strongly expressed membrane-bound Gfr alpha 1, and soluble Gfr alpha 1 was expressed within the lung mesenchyme, but only at early developmental stages. Together these findings indicate that the intrinsic innervation of the human lung is derived from the neural crest.