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首页> 外文期刊>Progress in brain research >Neurotrophin-3 in the development of the enteric nervous system.
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Neurotrophin-3 in the development of the enteric nervous system.

机译：Neurotrophin-3在肠神经系统的发育中。

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To date, the only neurotrophin that has been shown to influence the development of the enteric nervous system (ENS) is neurotrophin-3 (NT-3). NT-3 plays an essential role in the development of both the neural-crest-derived peripheral nervous system and the central nervous system (i.e., Chalazonitis, 1996, Mol. Neurobiol., 12: 39-53; Sieber-Blum, 1999, Neurotrophins and the Neural Crest, CRC Press, Boca Raton). This review integrates data obtained from our laboratory and from our collaboration with other investigators that demonstrate a late-acting role for NT-3 in the development of enteric neurons in vitro and in vivo. Studies of the biological actions of NT-3 on enteric neuronal precursors in vitro demonstrate that NT-3 acts directly on the precursor cells and that it also acts in combination with other neurotrophic factors such as glial cell line-derived neurotrophic factor and a ciliary neurotrophic factor-like molecule, to promote the survival and differentiation of enteric neurons and glia. Importantly, bone morphogenetic protein-2 (BMP-2) and BMP-4, members of the transforming growth factor-beta (TGF-beta) superfamily, regulate the onset of action of NT-3 during fetal gut development. Analyzes performed on mice deficient in the genes encoding NT-3 or its transducing tyrosine kinase receptor, TrkC, and conversely on transgenic mice that overexpress NT-3 substantiate a physiological role for NT-3 in the development and maintenance of a subset of enteric neurons. There is loss of neurons in both the myenteric and submucosal plexuses of mice lacking NT-3/TrkC signaling and selective hyperplasia in the myenteric plexus of mice overexpressing NT-3. Analyzes performed on transgenic mice that overexpress noggin, a specific BMP-4 antagonist, show significant decreases in the density of TrkC-expressing neurons but significant increase in overall neuronal density of both plexuses. Conversely, overexpression of BMP-4 is sufficient to produce, an increase in the proportion of TrkC-expressing neurons in both plexuses. Overall, our data point to a regulatory role of BMP-4 in the responses of subsets of myenteric and submucosal neurons to NT-3. NT-3 is required for the differentiation, maintenance and proper physiological function of late-developing enteric neurons that are important for the control of gut peristalsis.
机译：迄今为止，已显示影响肠道神经系统（ENS）发育的唯一神经营养蛋白是Neurotrophin-3（NT-3）。 NT-3在神经c衍生的周围神经系统和中枢神经系统的发育中都起着至关重要的作用（即Chalazonitis，1996; Mol.Neurobiol。，12：39-53; Sieber-Blum，1999，神经营养蛋白和神经the，CRC出版社，博卡拉顿）。这篇综述整合了从我们的实验室以及与其他研究人员的合作中获得的数据，这些数据证明了NT-3在体外和体内肠道神经元发育中的后期作用。 NT-3对肠道神经元前体的生物学作用的体外研究表明，NT-3直接作用于前体细胞，并且还与其他神经营养因子（如胶质细胞源性神经营养因子和睫状神经营养因子）联合作用因子样分子，促进肠道神经元和神经胶质细胞的存活和分化。重要的是，骨形态发生蛋白2（BMP-2）和BMP-4是转化生长因子β（TGF-beta）超家族的成员，在胎儿肠发育过程中调节NT-3的作用。对缺乏编码NT-3或其转导酪氨酸激酶受体TrkC的基因的小鼠进行的分析，反之，对过表达NT-3的转基因小鼠进行的分析证实了NT-3在一部分肠神经元的发育和维持中的生理作用。 。在缺乏NT-3 / TrkC信号传导的小鼠的肠系膜和粘膜下丛中均存在神经元丢失，而在过度表达NT-3的小鼠的肠系膜中则存在选择性增生。对过表达noggin（一种特定的BMP-4拮抗剂）的转基因小鼠进行的分析显示，表达TrkC的神经元密度显着降低，但两个神经丛的总体神经元密度显着提高。相反，BMP-4的过表达足以产生两个丛中TrkC表达神经元的比例增加。总体而言，我们的数据表明BMP-4在肌层和粘膜下神经元亚群对NT-3的应答中起调节作用。 NT-3是后期发育的肠神经元的分化，维持和正常生理功能所必需的，这对于控制肠蠕动很重要。

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