Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, Japan.
Brain Res. 2012 Oct 22;1480:30-40. doi: 10.1016/j.brainres.2012.08.055. Epub 2012 Sep 7.
The spinal nerve, which is composed of dorsal root ganglion (DRG) axons and spinal motor axons, divides into ventral and dorsal rami. Although the development of the ventral ramus has been examined in considerable detail, that of the dorsal ramus has not. Therefore, we first examined the spatial-temporal pattern of the dorsal ramus formation in the chick embryo, with special reference to the projection to the dermamyotome and its derivatives. Next, we focused on two guidance molecules, chick semaphorin 3A (SEMA3A) and fibroblast growth factor 8 (FGF8), because these are the best candidates as molecules for controlling the dorsal ramus formation. Using in situ hybridization and immunohistochemistry methods, we clearly showed a close relationship between the spatial-temporal expression of SEMA3A/FGF8 and the projection of dorsal ramus fibers to the dorsal muscles. We further examined the axonal response of motor and DRG neurons to SEMA3A and FGF8. We showed that motor axons responded to both SEMA3A-induced repulsion and FGF8-induced attraction. On the other hand, DRG axons responded to SEMA3A-induced repulsion but not to FGF8-induced attraction. These findings suggest that FGF8-induced attraction may guide early motor axons beneath the myotome and that SEMA3A-induced repulsion may prevent these early motor axons from entering the myotome. Our results also imply that the loss of SEMA3A expression in the dorsal muscles may lead to the gross projection of the dorsal ramus fibers into the dorsal muscles. Together, SEMA3A and FGF8 may contribute to the proper formation of the dorsal ramus.
脊神经由背根神经节(DRG)轴突和脊髓运动轴突组成,分为腹侧支和背侧支。虽然腹侧支的发育已经得到了相当详细的研究,但背侧支的发育尚未得到研究。因此,我们首先检查了鸡胚背侧支形成的时空模式,特别关注向真皮肌节及其衍生物的投射。接下来,我们集中研究了两个指导分子,鸡 Sema3A(SEMA3A)和成纤维细胞生长因子 8(FGF8),因为它们是控制背侧支形成的最佳候选分子。使用原位杂交和免疫组织化学方法,我们清楚地显示了 SEMA3A/FGF8 的时空表达与背侧支纤维向背侧肌肉投射之间的密切关系。我们进一步研究了运动和 DRG 神经元对 SEMA3A 和 FGF8 的轴突反应。我们表明,运动轴突对 SEMA3A 诱导的排斥和 FGF8 诱导的吸引都有反应。另一方面,DRG 轴突对 SEMA3A 诱导的排斥有反应,但对 FGF8 诱导的吸引没有反应。这些发现表明,FGF8 诱导的吸引可能指导肌节下的早期运动轴突,而 SEMA3A 诱导的排斥可能阻止这些早期运动轴突进入肌节。我们的结果还表明,背侧肌肉中 SEMA3A 表达的丧失可能导致背侧支纤维的大体投射进入背侧肌肉。总之,SEMA3A 和 FGF8 可能有助于背侧支的正常形成。