Saueressig H, Burrill J, Goulding M
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Development. 1999 Oct;126(19):4201-12. doi: 10.1242/dev.126.19.4201.
During early development, multiple classes of interneurons are generated in the spinal cord including association interneurons that synapse with motor neurons and regulate their activity. Very little is known about the molecular mechanisms that generate these interneuron cell types, nor is it known how axons from association interneurons are guided toward somatic motor neurons. By targeting the axonal reporter gene &tgr;-lacZ to the En1 locus, we show the cell-type-specific transcription factor Engrailed-1 (EN1) defines a population of association neurons that project locally to somatic motor neurons. These EN1 interneurons are born early and their axons pioneer an ipsilateral longitudinal projection in the ventral spinal cord. The EN1 interneurons extend axons in a stereotypic manner, first ventrally, then rostrally for one to two segments where their axons terminate close to motor neurons. We show that the growth of EN1 axons along a ventrolateral pathway toward motor neurons is dependent on netrin-1 signaling. In addition, we demonstrate that En1 regulates pathfinding and fasciculation during the second phase of EN1 axon growth in the ventrolateral funiculus (VLF); however, En1 is not required for the early specification of ventral interneuron cell types in the embryonic spinal cord.
在早期发育过程中，脊髓会产生多种类型的中间神经元，包括与运动神经元形成突触并调节其活动的联合中间神经元。对于产生这些中间神经元细胞类型的分子机制，我们知之甚少，而且也不清楚联合中间神经元的轴突是如何被导向躯体运动神经元的。通过将轴突报告基因β-半乳糖苷酶靶向到En1基因座，我们发现细胞类型特异性转录因子Engrailed-1（EN1）定义了一群向躯体运动神经元进行局部投射的联合神经元。这些EN1中间神经元早期产生，其轴突在脊髓腹侧开辟了一条同侧纵向投射通路。EN1中间神经元以一种刻板的方式延伸轴突，首先向腹侧延伸，然后向头侧延伸一到两个节段，其轴突在靠近运动神经元的位置终止。我们发现，EN1轴突沿着腹外侧通路向运动神经元生长依赖于netrin-1信号传导。此外，我们证明En1在EN1轴突在腹外侧索（VLF）生长的第二阶段调节路径寻找和束状化；然而，En1对于胚胎脊髓中腹侧中间神经元细胞类型的早期特化并非必需。
