Steffensky Marion, Steinbach Karin, Schwarz Uli, Schlosshauer Burkhard
NMI Naturwissenschaftliches und Medizinisches Institut, an der Universität Tübingen, Markwiesenstr. 55, D-72770 Reutlingen, Germany.
Int J Dev Neurosci. 2006 Feb;24(1):65-72. doi: 10.1016/j.ijdevneu.2005.10.007. Epub 2005 Dec 9.
During the development of the central nervous system (CNS), the correct wiring of outgrowing neurites is mediated by antagonistic mechanisms. Aberrant growth is prevented by repulsive factors such as semaphorins. Expression of the ligands Sema3A and -3E and the receptors neuropilin Npn-1, -2a and -2b in the chick visual system were analyzed by RT-PCR. Whereas Sema3A and its major receptor Npn-1 were abundant, Sema3E and Npn-2 isoform expression was highly restricted and developmentally regulated. Peak expression occurred during retinal axon innervation of the tectum. Functional in vitro assays with recombinant proteins revealed a topography-specific growth cone collapsing activity of Sema3A for tectal axons. Interestingly, whereas tectal axons collapsed in a topographic-specific manner only in the presence of Sema3A, retinal axons responded only to Sema3E. The collapsing activity was intracellularly mediated by cGMP. For a detailed analysis of neuronal responses to sempahorins, time lapse video recording was performed. When tectal and retinal axons were pre-exposed to brain-derived neurotrophic factor (BDNF), a protective effect was evident only in the case of retinal axons. Our results suggest a molecular mechanism whereby ingrowth of retinal axons into the tectum can be regulated by Sema3E/BDNF modulation without disturbing tectal axon growth out of the tectum mediated by Sema3A.
在中枢神经系统（CNS）发育过程中，生长中的神经突的正确布线由拮抗机制介导。诸如信号素等排斥因子可防止异常生长。通过逆转录聚合酶链反应（RT-PCR）分析了鸡视觉系统中配体Sema3A和-3E以及受体神经纤毛蛋白Npn-1、-2a和-2b的表达。虽然Sema3A及其主要受体Npn-1含量丰富，但Sema3E和Npn-2亚型的表达受到高度限制且受发育调控。在视网膜轴突支配顶盖期间出现表达峰值。用重组蛋白进行的体外功能试验显示，Sema3A对顶盖轴突具有地形特异性的生长锥塌陷活性。有趣的是，虽然顶盖轴突仅在存在Sema3A的情况下以地形特异性方式塌陷，但视网膜轴突仅对Sema3E有反应。塌陷活性由细胞内的环鸟苷酸（cGMP）介导。为了详细分析神经元对信号素的反应，进行了延时视频记录。当顶盖和视网膜轴突预先暴露于脑源性神经营养因子（BDNF）时，仅在视网膜轴突的情况下有明显的保护作用。我们的结果提示了一种分子机制，通过这种机制，视网膜轴突向顶盖的长入可通过Sema3E/BDNF调节来控制，而不会干扰由Sema3A介导的顶盖轴突从顶盖向外的生长。
