Jessberger Sebastian, Aigner Stefan, Clemenson Gregory D, Toni Nicolas, Lie D Chichung, Karalay Ozlem, Overall Rupert, Kempermann Gerd, Gage Fred H
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA.
PLoS Biol. 2008 Nov 11;6(11):e272. doi: 10.1371/journal.pbio.0060272.
Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5) activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.
新生颗粒细胞在经历形态学和电生理学成熟过程后，在功能上整合到成年齿状回的突触回路中。未成熟神经元及其伸出的神经突找到其合适位置和靶区域的分子机制在很大程度上仍不清楚。在此我们表明，使用基于逆转录病毒的策略在新生细胞中对细胞周期蛋白依赖性激酶5（cdk5）活性进行单细胞特异性敲低会导致树突状突起异常生长，这与新生细胞迁移模式改变有关。尽管在cdk5缺陷细胞中棘突形成和成熟减少，但异常树突在门区神经元上形成异位突触。这些观察结果表明cdk5在成体神经发生过程中新生神经元的成熟和树突延伸中起关键作用。这里呈现的数据还表明在精确的树突靶向和随后的突触形成之间存在机制上的分离。
