Neuronal Basic Helix-Loop-Helix Proteins Neurod2/6 Regulate Cortical Commissure Formation before Midline Interactions
Neuronal Basic Helix-Loop-Helix Proteins Neurod2/6 Regulate Cortical Commissure Formation before Midline Interactions
复制标题
DOI：
10.1523/jneurosci.0899-12.2013
复制
发表时间：
2013-01-09
影响因子：
5.3
通讯作者：
Schwab, Markus H.
中科院分区：
文献类型：
--
作者：
Bormuth, Ingo;Yan, Kuo;Schwab, Markus H.
新皮层投射神经元建立远端纤维束是大脑高级功能的基础。然而，轴突束形成的分子控制仍然知之甚少。在这里，我们已经确定了基本螺旋-环-螺旋（bHLH）转录因子Neurod2和Neurod6是小鼠新皮层中束状化和靶向轴生的关键调节因子。在Neurod2/6双突变小鼠中，胼胝体轴突缺乏细胞粘附分子contact2的表达，在室下区无血循环，不能向中线生长而不形成Probst束。相反，突变的轴突过度表达Robo1，并遵循随机轨迹进入同侧皮层。与长期轴突发生相反，锥体神经元的产生和维持以及最初的轴突生长是非常正常的，这表明这些过程受到不同的转录控制。我们的发现定义了胼胝体发育的一个新阶段，并证明新皮层投射神经元需要神经元bHLH蛋白的转录规范来执行一个内在的远程连接程序。
Establishment of long-range fiber tracts by neocortical projection neurons is fundamental for higher brain functions. The molecular control of axon tract formation, however, is still poorly understood. Here, we have identified basic helix-loop-helix (bHLH) transcription factors Neurod2 and Neurod6 as key regulators of fasciculation and targeted axogenesis in the mouse neocortex. In Neurod2/6 double-mutant mice, callosal axons lack expression of the cell adhesion molecule Contactin2, defasciculate in the subventricular zone, and fail to grow toward the midline without forming Probst bundles. Instead, mutant axons overexpress Robo1 and follow random trajectories into the ipsilateral cortex. In contrast to long-range axogenesis, generation and maintenance of pyramidal neurons and initial axon outgrowth are grossly normal, suggesting that these processes are under distinct transcriptional control. Our findings define a new stage in corpus callosum development and demonstrate that neocortical projection neurons require transcriptional specification by neuronal bHLH proteins to execute an intrinsic program of remote connectivity.