Ince-Dunn Gulayse, Hall Benjamin J, Hu Shu-Ching, Ripley Beth, Huganir Richard L, Olson James M, Tapscott Stephen J, Ghosh Anirvan
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 2006 Mar 2;49(5):683-95. doi: 10.1016/j.neuron.2006.01.031.
During cortical development, both activity-dependent and genetically determined mechanisms are required to establish proper neuronal connectivity. While activity-dependent transcription may link the two processes, specific transcription factors that mediate such a process have not been identified. We identified the basic helix-loop-helix (bHLH) transcription factor Neurogenic Differentiation 2 (NeuroD2) in a screen for calcium-regulated transcription factors and report that it is required for the proper development of thalamocortical connections. In neuroD2 null mice, thalamocortical axon terminals fail to segregate in the somatosensory cortex, and the postsynaptic barrel organization is disrupted. Additionally, synaptic transmission is defective at thalamocortical synapses in neuroD2 null mice. Total excitatory synaptic currents are reduced in layer IV in the knockouts, and the relative contribution of AMPA and NMDA receptor-mediated currents to evoked responses is decreased. These observations indicate that NeuroD2 plays a critical role in regulating synaptic maturation and the patterning of thalamocortical connections.
在皮质发育过程中，需要依赖活动和由基因决定的机制来建立适当的神经元连接。虽然依赖活动的转录可能将这两个过程联系起来，但尚未确定介导这一过程的特定转录因子。我们在筛选钙调节转录因子时鉴定出了碱性螺旋-环-螺旋（bHLH）转录因子神经源性分化2（NeuroD2），并报告它是丘脑皮质连接正常发育所必需的。在NeuroD2基因敲除小鼠中，丘脑皮质轴突终末无法在体感皮层中分离，并且突触后桶状结构被破坏。此外，NeuroD2基因敲除小鼠的丘脑皮质突触处的突触传递存在缺陷。基因敲除小鼠的IV层中总的兴奋性突触电流减少，并且AMPA和NMDA受体介导的电流对诱发反应的相对贡献降低。这些观察结果表明，NeuroD2在调节突触成熟和丘脑皮质连接模式中起关键作用。
