BMP signaling regulates murine enteric nervous system precursor migration, neurite fasciculation, and patterning via altered Ncam1 polysialic acid addition
BMP signaling regulates murine enteric nervous system precursor migration, neurite fasciculation, and patterning via altered Ncam1 polysialic acid addition
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DOI：
10.1016/j.ydbio.2006.07.016
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发表时间：
2006-11-01
影响因子：
2.7
通讯作者：
Heuckeroth, Robert O.
中科院分区：
文献类型：
--
作者：
Fu, Ming;Vohra, Bhupinder P. S.;Heuckeroth, Robert O.
肠神经系统（ENS）由迁移的神经嵴衍生的前体形成，所述前体分化成神经元和神经胶质，聚集成神经节细胞簇，并延伸神经元过程以形成控制肠功能的许多方面的复杂的相互作用网络。骨形态发生蛋白（BMPs）在发育中具有不同的作用，并影响ENS前体的分化、增殖和存活。我们假设BMP信号传导可能对ENS前体迁移、神经节细胞聚集和形成肠神经系统所必需的神经突成束也很重要。我们现在证明，BMP信号限制小鼠ENS前体肠壁迁移过程中。此外，阻断BMP信号传导导致鼠结肠的更快定殖，减少神经节细胞聚集，并减少神经突成束。BMP信号传导也影响发育中肠壁内神经突延伸的模式。这些对ENS前体迁移和神经突成束的影响似乎至少部分是通过增加聚唾液酸来介导的，除了神经细胞粘附分子（Ncam 1）响应BMP。去除PSA酶促逆转BMP对ENS前体迁移和神经突成束的影响。这些研究证明了BMP信号传导的几种新作用，并强调了唾液酸转移酶在发展中的ENS中的新功能。All rights reserved.
The enteric nervous system (ENS) forms from migrating neural crest-derived precursors that differentiate into neurons and glia, aggregate into ganglion cell clusters, and extend neuronal processes to form a complex interacting network that controls many aspects of intestinal function. Bone morphogenetic proteins (BMPs) have diverse roles in development and influence the differentiation, proliferation, and survival of ENS precursors. We hypothesized that BMP signaling might also be important for the ENS precursor migration, ganglion cell aggregation, and neurite fasciculation necessary to form the enteric nervous system. We now demonstrate that BMP signaling restricts murine ENS precursors to the outer bowel wall during migration. In addition, blocking BMP signaling causes faster colonization of the murine colon, reduces ganglion cell aggregation, and reduces neurite fasciculation. BMP signaling also influences patterns of neurite extension within the developing bowel wall. These effects on ENS precursor migration and neurite fasciculation appear to be mediated at least in part by increased polysialic acid addition to neural cell adhesion molecule (Ncam1) in response to BMP. Removing PSA enzymatically reverses the BMP effects on ENS precursor migration and neurite fasciculation. These studies demonstrate several novel roles for BMP signaling and highlight new functions for sialyltransferases in the developing ENS. (c) 2006 Elsevier Inc. All rights reserved.