Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Development. 2011 Sep;138(18):4085-95. doi: 10.1242/dev.066076. Epub 2011 Aug 10.
Different types of sensory neurons in the dorsal root ganglia project axons to the spinal cord to convey peripheral information to the central nervous system. Whereas most proprioceptive axons enter the spinal cord medially, cutaneous axons typically do so laterally. Because heavily myelinated proprioceptive axons project to the ventral spinal cord, proprioceptive axons and their associated oligodendrocytes avoid the superficial dorsal horn. However, it remains unclear whether their exclusion from the superficial dorsal horn is an important aspect of neural circuitry. Here we show that a mouse null mutation of Sema6d results in ectopic placement of the shafts of proprioceptive axons and their associated oligodendrocytes in the superficial dorsal horn, disrupting its synaptic organization. Anatomical and electrophysiological analyses show that proper axon positioning does not seem to be required for sensory afferent connectivity with motor neurons. Furthermore, ablation of oligodendrocytes from Sema6d mutants reveals that ectopic oligodendrocytes, but not proprioceptive axons, inhibit synapse formation in Sema6d mutants. Our findings provide new insights into the relationship between oligodendrocytes and synapse formation in vivo, which might be an important element in controlling the development of neural wiring in the central nervous system.
背根神经节中的不同类型感觉神经元将轴突投射到脊髓，将外周信息传递到中枢神经系统。虽然大多数本体感觉轴突向内侧进入脊髓，但皮肤轴突通常向外侧进入。由于高度髓鞘化的本体感觉轴突投射到脊髓腹侧，本体感觉轴突及其相关的少突胶质细胞避免了浅层背角。然而，它们是否被排除在浅层背角之外仍然是神经回路的一个重要方面尚不清楚。在这里，我们展示了 Sema6d 基因敲除小鼠的轴突和相关少突胶质细胞在浅层背角中的异位放置，破坏了其突触组织。解剖学和电生理学分析表明，感觉传入与运动神经元的连接似乎不需要适当的轴突定位。此外，Sema6d 突变体中少突胶质细胞的消融表明，异位少突胶质细胞而非本体感觉轴突抑制了 Sema6d 突变体中的突触形成。我们的发现为体内少突胶质细胞与突触形成之间的关系提供了新的见解，这可能是控制中枢神经系统神经布线发育的重要因素。
