Sacral neural crest cells colonise aganglionic hindgut in vivo but fail to compensate for lack of enteric ganglia
Sacral neural crest cells colonise aganglionic hindgut in vivo but fail to compensate for lack of enteric ganglia
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DOI：
10.1006/dbio.1999.9592
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发表时间：
2000-03-01
影响因子：
2.7
通讯作者：
Le Douarin, NM
中科院分区：
文献类型：
--
作者：
Burns, AJ;Champeval, D;Le Douarin, NM
迷走神经嵴是构成肠神经系统的大多数神经元和神经胶质的起源，是肠道的内在神经支配。我们最近证实，神经轴的第二个区域，即骶神经嵴，也对雏鸡的肌间神经丛和粘膜下丛的肠神经元和神经胶质细胞群做出贡献，尾部到脐水平。先前的研究结果表明，在迷走神经来源的细胞完成沿整个肠道的迁移后仅 4 天，骶神经嵴来源的前体细胞就在肠道中大量定植。这一观察结果表明，为了迁移到后肠并分化为肠神经元和神经胶质细胞，骶神经嵴细胞可能需要与迷走神经衍生细胞或它们或其后代释放的因子或信号分子相互作用。这种相互依赖性也可以解释为什么骶神经嵴细胞无法补偿人类先天性巨结肠或动物无神经节巨结肠的终末后肠神经节的缺乏。为了研究后肠内骶神经和迷走神经源性神经嵴细胞之间可能的相互关系，我们绘制了各种迷走神经嵴区域对肠道的贡献，然后消融雏鸡迷走神经嵴的适当部分以中断肠神经系统前体细胞的迁移，从而在体内创建无神经节后肠模型。在这些相同的消融动物中，骶神经轴被移除并用来自鹌鹑胚胎的等效组织代替，从而使我们能够使用细胞特异性抗体记录骶嵴衍生细胞的迁移和分化。结果表明，迷走神经嵴以区域化方式贡献了肠神经系统的前体。当对邻近体节 1-2 的鹌鹑雏鸡神经管进行移植时，在整个脐前肠道的肠神经节中发现了神经嵴细胞。这些细胞在食道中数量最多，在脐前肠中稀疏，在脐后肠道中不存在。当在体节 3-5 或 3-6 附近进行类似的移植时，在整个肠道（从近端食管到远端结肠）的肠神经节内发现了嵴细胞。邻近 6-7 体节的迷走神经嵴移植物显示，来自该区域的嵴细胞沿尾-喙梯度分布，在后肠中数量最多，在肠道中较少，并且在近端前肠中不存在。为了在体内产生神经后肠，有必要在 13 体节发育阶段之前消融与 3-6 体节相邻的迷走神经嵴。当进行这种消融时，后肠（在某些情况下还有盲肠区域）缺乏肠神经节丛。这些迷走神经嵴消融雏鸡的骶神经嵴移植表明，骶细胞沿着正常的、先前描述的后肠途径迁移，并在假定的肌间神经丛和粘膜下神经丛的水平形成含有神经元和神经胶质细胞的孤立神经节。迷走神经嵴消融和未消融对照动物之间的比较表明，在消融动物中，骶神经嵴衍生的细胞迁移到肠道中并分化为神经元，其数量高于对照组。然而，后肠内骶神经嵴衍生神经元数量的增加似乎不足以补偿迷走神经衍生肠丛的缺乏，因为含有骶神经嵴衍生神经元和神经胶质细胞的神经节被小且不常见。我们的研究结果表明，相对固定的骶神经嵴细胞亚群的神经元命运可能是预先确定的，因为这些细胞既不需要迷走神经源性肠前体细胞的存在来定殖后肠，也不能够显着改变它们的增殖或分化。 (C) 2000 年学术出版社。
The vagal neural crest is the origin of majority of neurons and glia that constitute the enteric nervous system, the intrinsic innervation of the gut. We have recently confirmed that a second region of the neuraxis, the sacral neural crest, also contributes to the enteric neuronal and glial populations of both the myenteric and the submucosal plexuses in the chick, caudal to the level of the umbilicus. Results from this previous study showed that sacral neural crest-derived precursors colonised the gut in significant numbers only 4 days after vagal derived cells had completed their migration along the entire length of the gut. This observation suggested that in order to migrate into the hindgut and differentiate into enteric neurons and glia, sacral neural crest cells may require an interaction with vagal-derived cells or with factors or signalling molecules released by them or their progeny. This interdependence may also explain the inability of sacral neural crest cells to compensate for the lack of ganglia in the terminal hindgut of Hirschsprung's disease in humans or aganglionic megacolon in animals. To investigate the possible interrelationship between sacral and vagal derived neural crest cells within the hindgut, we mapped the contribution of various vagal neural crest regions to the gut and then ablated appropriate sections of chick vagal neural crest to interrupt the migration of enteric nervous system precursor cells and thus create an aganglionic hindgut model in vivo. In these same ablated animals, the sacral level neural axis was removed and replaced with the equivalent tissue from quail embryos, thus enabling us to document, using cell-specific antibodies, the migration and differentiation of sacral crest-derived cells. Results showed that the vagal neural crest contributed precursors to the enteric nervous system in a regionalised manner. When quail-chick grafts of the neural tube adjacent to somites 1-2 were performed, neural crest cells were found in enteric ganglia throughout the preumbilical gut. These cells were most numerous in the esophagus, sparse in the preumbilical intestine, and absent in the postumbilical gut. When similar grafts adjacent to somites 3-5 or 3-6 were carried out, crest cells were found within enteric ganglia along the entire gut, from the proximal esophagus to the distal colon. Vagal neural crest grafts adjacent to somites 6-7 showed that crest cells from this region were distributed along a caudal-rostral gradient, being most numerous in the hindgut, less so in the intestine, and absent in the proximal foregut. In order to generate aneural hindgut in vivo, it was necessary to ablate the vagal neural crest adjacent to somites 3-6, prior to the 13-somite stage of development. When such ablations were performed, the hindgut, and in some cases also the cecal region, lacked enteric ganglionated plexuses. Sacral neural crest grafting in these vagal neural crest ablated chicks showed that sacral cells migrated along normal, previously described hindgut pathways and formed isolated ganglia containing neurons and glia at the levels of the presumptive myenteric and submucosal plexuses. Comparison between vagal neural crest-ablated and nonablated control animals demonstrated that sacral-derived cells migrated into the gut and differentiated into neurons in higher numbers in the ablated animals than in controls.However, the increase in numbers of sacral neural crest-derived neurons within the hindgut did not appear to be sufficiently high to compensate for the lack of vagal-derived enteric plexuses, as ganglia containing sacral neural crest-derived neurons and glia were small and infrequent. Our findings suggest that the neuronal fate of a relatively fixed subpopulation of sacral neural crest cells may be predetermined as these cells neither require the presence of vagal derived enteric precursors in order to colonise the hindgut, nor are capable of dramatically altering their proliferation or differentiation. (C) 2000 Academic Press.