Bronner-Fraser M, Wolf J J, Murray B A
Developmental Biology Center, University of California, Irvine 92717.
Dev Biol. 1992 Oct;153(2):291-301. doi: 10.1016/0012-1606(92)90114-v.
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 tube in 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.
我们研究了特定细胞黏附分子N-钙黏蛋白和神经细胞黏附分子（N-CAM）在体内颅神经嵴细胞从神经管迁出过程中的分布及功能。通过免疫细胞化学分析，在神经管闭合前，颅神经褶上可检测到N-钙黏蛋白和N-CAM。神经管闭合后，神经管背侧的假定颅神经嵴细胞具有明亮的N-CAM免疫反应性和较弱的N-钙黏蛋白免疫反应性。到10至11体节期时，除了最背侧的细胞几乎没有或没有可检测到的免疫反应性外，N-钙黏蛋白在所有神经管细胞上都很突出。一些迁移的神经嵴细胞从颅神经管迁出后，可观察到N-CAM，但未观察到N-钙黏蛋白。为了研究这些分子的功能意义，通过将抗N-CAM或N-钙黏蛋白的抗体注射到中脑附近的颅间充质中进行了干扰实验。抗N-CAM单克隆和多克隆抗体的Fab片段或完整IgG导致颅神经管和神经嵴出现异常。主要观察到的缺陷包括神经管内外异位位置的神经嵴细胞，以及含有一些解离细胞的轻度变形的神经管。一种抗N-钙黏蛋白单克隆抗体也破坏了颅部发育，主要缺陷是神经管严重扭曲和神经管外一些异位神经嵴细胞存在。相比之下，非阻断性N-CAM抗体和对照IgG几乎没有影响。从神经褶到9体节期的有限发育时期内，胚胎似乎对N-CAM和N-钙黏蛋白抗体敏感，抗体注射后较老的胚胎不再出现缺陷。这些结果表明，细胞黏附分子N-CAM和N-钙黏蛋白对于颅神经管的正常完整性以及神经嵴细胞的迁出很重要。由于颅神经嵴细胞的正常迁出也需要细胞与基质的相互作用，结果表明细胞间和细胞与基质黏附之间的平衡对于这个过程可能至关重要。
