De Vries Melissa, Cooper Helen M
The Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
J Neurochem. 2008 Aug;106(4):1483-92. doi: 10.1111/j.1471-4159.2008.05485.x. Epub 2008 May 15.
It is now well established that the netrin guidance cues and their receptors comprise a major molecular guidance system driving axon pathfinding during nervous system development. One netrin receptor, neogenin, is now emerging as a key regulator of many developmental processes throughout the embryo. Unexpectedly, a new family of neogenin ligands, the repulsive guidance molecule (RGM) family, has recently been identified. The functional outcome of neogenin activation is dictated by both the nature of the ligand as well as the developmental context. Netrin-1-neogenin interactions mediate chemoattractive axon guidance, while RGMa-neogenin interactions repel axons. Neogenin is required for the establishment of the pseudostratified epithelium of the neural tube, probably by promoting cell adhesion. In addition, a role for RGMa and neogenin in neuronal differentiation has been demonstrated. While neogenin signaling cascades are poorly understood, the opposing responses of neogenin to RGMa and netrin-1 in the context of axon guidance indicates that neogenin signaling is complex and subject to tight spatiotemporal regulation. In summary, neogenin is a multifunctional receptor regulating diverse developmental processes. Thus, its contribution to neural development is proving to be considerably more extensive than originally predicted.
现已充分证实，网蛋白导向线索及其受体构成了神经系统发育过程中驱动轴突寻路的主要分子导向系统。一种网蛋白受体——新基因蛋白，正逐渐成为整个胚胎许多发育过程的关键调节因子。出乎意料的是，最近发现了一个新的新基因蛋白配体家族——排斥性导向分子（RGM）家族。新基因蛋白激活的功能结果取决于配体的性质以及发育环境。Netrin-1与新基因蛋白的相互作用介导化学吸引性轴突导向，而RGMa与新基因蛋白的相互作用则排斥轴突。新基因蛋白可能通过促进细胞黏附来参与神经管假复层上皮的形成。此外，已经证明RGMa和新基因蛋白在神经元分化中发挥作用。虽然对新基因蛋白信号级联的了解甚少，但在轴突导向背景下新基因蛋白对RGMa和Netrin-1的相反反应表明，新基因蛋白信号传导很复杂，且受到严格的时空调节。总之，新基因蛋白是一种调节多种发育过程的多功能受体。因此，它对神经发育的贡献比最初预测的要广泛得多。
