EFFECTS OF ANTIBODIES AGAINST N-CADHERIN AND N-CAM ON THE CRANIAL NEURAL CREST AND NEURAL-TUBE
EFFECTS OF ANTIBODIES AGAINST N-CADHERIN AND N-CAM ON THE CRANIAL NEURAL CREST AND NEURAL-TUBE
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DOI：
10.1016/0012-1606(92)90114-v
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发表时间：
1992-10-01
影响因子：
2.7
通讯作者：
MURRAY, BA
中科院分区：
文献类型：
--
作者：
BRONNERFRASER, M;WOLF, JJ;MURRAY, BA
我们研究了神经嵴细胞在神经管中迁移过程中细胞粘附分子N-cadherin和N-CAM的分布和功能。通过免疫细胞化学分析，N-cadherin和N-CAM均在神经管闭合前的颅神经褶皱上被检测到。关闭后的神经管，假定颅神经嵴细胞内的神经管的背面有明亮的N-CAM和弱的N-cadherin免疫反应。由10至11体节阶段，N-钙粘蛋白是突出的所有神经管细胞与最背侧的细胞，其中有很少或根本没有检测到的免疫反应性除外。N-CAM，而不是N-cadherin，观察到一些迁移的神经嵴细胞离开颅神经管后。为了检查这些分子的功能意义，扰动实验进行注射抗体对N-CAM或N-钙粘蛋白到邻近中脑的颅间充质。抗N-CAM的单克隆和多克隆抗体的Fab '片段或完整IgG引起颅神经管和神经嵴的异常。主要观察到的缺陷包括异位位置的神经嵴细胞，包括神经管内外，以及含有一些游离细胞的轻度变形的神经管。抗N-钙粘蛋白的单克隆抗体也破坏了颅骨发育，主要缺陷是严重扭曲的神经管和神经管外的一些异位神经嵴细胞。相比之下，非阻断N-CAM抗体和对照IgG几乎没有影响。胚胎似乎是敏感的N-CAM和N-cadherin抗体从神经折叠到9-体节阶段的一个有限的发展时期，与较老的胚胎不再显示抗体注射后的缺陷。这些结果表明，细胞粘附分子N-CAM和N-cadherin是重要的颅神经管的正常完整性和神经嵴细胞的迁移。由于细胞-基质相互作用也需要颅神经嵴细胞的适当迁移，结果表明，细胞-细胞和细胞-基质粘附之间的平衡可能是这个过程的关键。
We have examined the distribution and function of the defined cell adhesion molecules, N-cadherin and N-CAM, in the emigration of cranial neural crest cells from the neural tubein vivo. By immunocytochemical analysis, both N-cadherin and N-CAM were detected on the cranial neural folds prior to neural tube closure. After closure of the neural tube, presumptive cranial neural crest cells within the dorsal aspect of the neural tube had bright N-CAM and weak N-cadherin immunoreactivity. By the 10- to 11-somite stage, N-cadherin was prominent on all neural tube cells with the exception of the dorsal-most cells, which had little or no detectable immunoreactivity. N-CAM, but not N-cadherin, was observed on some migrating neural crest cells after their departure from the cranial neural tube. To examine the functional significance of these molecules, perturbation experiments were performed by injecting antibodies against N-CAM or N-cadherin into the cranial mesenchyme adjacent to the midbrain. Fab' fragments or whole IgGs of monoclonal and polyclonal antibodies against N-CAM caused abnormalities in the cranial neural tube and neural crest. Predominantly observed defects included neural crest cells in ectopic locations, both within and external to the neural tube, and mildly deformed neural tubes containing some dissociating cells. A monoclonal antibody against N-cadherin also disrupted cranial development, with the major defect being grossly distorted neural tubes and some ectopic neural crest cells outside of the neural tube. In contrast, nonblocking N-CAM antibodies and control IgGs had few effects. Embryos appeared to be sensitive to the N-CAM and N-cadherin antibodies for a limited developmental period from the neural fold to the 9-somite stage, with older embryos no longer displaying defects after antibody injection. These results suggest that the cell adhesion molecules N-CAM and N-cadherin are important for the normal integrity of the cranial neural tube and for the emigration of neural crest cells. Because cell-matrix interactions also are required for proper emigration of cranial neural crest cells, the results suggest that the balance between cell-cell and cell-matrix adhesion may be critical for this process.