Migration of LHRH neurons from nasal to forebrain region--an analysis of molecular mechanisms of neuronal migration

嗅板切除后，LHRH免疫反应阳性细胞未到达前脑，提示嗅神经（ON）束的中枢投射是LHRH神经元正常迁移到鸡胚前脑的先决条件。LHRH神经元偏离其正常的迁移路线，迁移到眼神经内侧分支，该分支对高度多聚唾液酸化的NCAM（NCAM-H）呈阳性。这种迁移性LHRH神经元的游离现象表明，这些游离的LHRH神经元的迁移需要一定的结构支持，其迁移路线和命运并不完全由嗅板中的前体细胞所决定。在6周胚胎中，LHRH神经元位于犁鼻器原基对应的嗅上皮内侧部、犁鼻器终末神经复合体内侧部和前脑腹侧。这些神经元强烈表达NCAM-H。在体内和体外研究，包括那些对人类胚胎，迁移LHRH神经元和NCAM-H表达的神经元的共存总是得到证实。近年来，在LHRH神经元的迁移过程中，在LHRH神经元、嗅上皮、视上核和腹侧前脑中发现了一种神经蛋白聚糖（6 B4蛋白聚糖/磷酸蛋白聚糖），即细胞表面相关的细胞外基质。由于已知phosphacan结合NCAM，因此phosphacan与NCAM的结合可能参与胚胎发育期间LHRH神经元从鼻到前脑区域的迁移。

No LHRH-immunoreactive cells arrive into the forebrain following olfactory placodectomy, suggesting that the availability of the central projection of the olfactory nerve (ON) bundle is prerequisite for the normal migration of LHRH neurons into the forebrain in chick embryos.In the cases in which the central projection of the ON is absent, LHRH neurons are deviated from their regular migratory course to the medial branch of ophthalmic nerve which is positive to highly polysialylated NCAM (NCAM-H). This straying phenomenon of migrating LHRH neurons indicates that some structural support are needed for the migration of these straying LHRH neurons, and suggests that their migratory route and destiny are not completely programd in their precursor cells in the olphactory placode.In the studies on human embryos, LHRH neurons are not detectable in the 5w-embryos. In the 6w-embryos, LHRH neurons in the medial part of the olfactory epithelium corresponding to the vomeronasal organ anlage, the medial part of the ON-vomeronasal-terminal nerve complex and in the ventral forebrain. These neural elements strongly express NCAM-H.In vivo and in vitro studies including those on human embryos, the coexistence of migrating LHRH neurons and NCAM-H-expressing neural elements is always confirmed. Recently, a neural proteoglycan (6B4 proteoglycan/phosphacan), cell surface-associated extracellular matrix, is found in the LHRH neurons, the olfactory epithelium, the ON and the ventral forebrain during ther migration of LHRH neurons. Since phosphacan is known to bind NCAM,it is possible that the binding of phosphacan with NCAM may be involved in the migration of LHRH neurons from the nasal to forebrain region during embryonic development.