Gaudillière Brice, Konishi Yoshiyuki, de la Iglesia Núria, Yao Gui lan, Bonni Azad
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2004 Jan 22;41(2):229-41. doi: 10.1016/s0896-6273(03)00841-9.
The elaboration of dendrites is fundamental to the establishment of neuronal polarity and connectivity, but the mechanisms that underlie dendritic morphogenesis are poorly understood. We found that the genetic knockdown of the transcription factor NeuroD in primary granule neurons including in organotypic cerebellar slices profoundly impaired the generation and maintenance of dendrites while sparing the development of axons. We also found that NeuroD mediated neuronal activity-dependent dendritogenesis. The activity-induced protein kinase CaMKII catalyzed the phosphorylation of NeuroD at distinct sites, including endogenous NeuroD at Ser336 in primary neurons, and thereby stimulated dendritic growth. These findings uncover an essential function for NeuroD in granule neuron dendritic morphogenesis. Our study also defines the CaMKII-NeuroD signaling pathway as a novel mechanism underlying activity-regulated dendritic growth that may play important roles in the developing and mature brain.
树突的形成对于神经元极性和连接性的建立至关重要，但树突形态发生的潜在机制却知之甚少。我们发现，在包括小脑器官型切片中的初级颗粒神经元中，转录因子NeuroD的基因敲低严重损害了树突的生成和维持，而轴突的发育则不受影响。我们还发现NeuroD介导神经元活动依赖性的树突形成。活动诱导的蛋白激酶CaMKII催化NeuroD在不同位点的磷酸化，包括初级神经元中Ser336位点的内源性NeuroD，从而刺激树突生长。这些发现揭示了NeuroD在颗粒神经元树突形态发生中的重要功能。我们的研究还将CaMKII-NeuroD信号通路定义为一种新的活动调节树突生长的机制，该机制可能在发育中和成熟的大脑中发挥重要作用。
