期刊
JOURNAL OF NEUROSCIENCE
卷 33, 期 2, 页码 641-651出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0899-12.2013
关键词
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资金
- German Research Foundation Excellence Cluster NeuroCure [Exc 257]
- Heisenberg Program
- German Research Foundation Research Center of Molecular Physiology of the Brain
- German Research Foundation [SFB-TRR 58 TP A08]
- National Institute of Child Health and Human Development
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.
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