Misplacement of Purkinje cells during postnatal development in Bax knock-out mice: A novel role for programmed cell death in the nervous system?
Misplacement of Purkinje cells during postnatal development in Bax knock-out mice: A novel role for programmed cell death in the nervous system?
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DOI：
10.1523/jneurosci.3897-07.2008
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发表时间：
2008-03-12
影响因子：
5.3
通讯作者：
Sun, Woong
中科院分区：
文献类型：
--
作者：
Jung, A-rong;Kim, Tae Woo;Sun, Woong
在出生后早期发育过程中，神经元的增殖、迁移和存活与消除的协调调节对小脑的组织发生至关重要。例如，浦肯野细胞（Purkinje cells, PCs）促进外颗粒细胞（EGCs）的增殖和迁移，而EGCs反过来又在浦肯野细胞的迁移中发挥作用。考虑到大量的神经元在小脑发育过程中经历程序性细胞死亡（PCD），神经元损失似乎在小脑的组织发生中起着重要作用。为了解决这个问题，我们研究了bax敲除（KO）小鼠的出生后小脑发育，其中PC的PCD被选择性地减少或消除，而EGCs则不受影响。我们在Bax-KO小鼠中证实了pcpcd的缺失以及EGCs的正常PCD。我们还观察到，在出生后第5天（P5）至P10天，在Bax-KO小鼠的内颗粒细胞层中有一个PC亚群错位，并且在小脑组织发生的主要时期（P14）结束时，PC标记calbindin的表达丧失。这些结果表明，去除异位神经元可能是发育性PCD的一个以前未被认识的功能。
During early postnatal development, the orchestrated regulation of proliferation, migration and the survival versus elimination of neurons is essential for histogenesis of the cerebellum. For instance, Purkinje cells (PCs) promote the proliferation and migration of external granule cells (EGCs), whereas EGCs in turn play a role in the migration of PCs. Considering that a substantial number of neurons undergo programmed cell death (PCD) during cerebellar development, it seems likely that neuronal loss could have a significant role in the histogenesis of the cerebellum. To address this question, we examined postnatal development of the cerebellum in Bax-knock-out (KO) mice in which the PCD of PC has been reported to be selectively reduced or eliminated, whereas EGCs are unaffected. We confirmed the absence of PC PCD as well as the normal PCD of EGCs in Bax-KO mice. We also observed a subpopulation of PCs that were misplaced in the inner granule cell layer of Bax-KO mice on postnatal day 5 (P5) to P10 and that, by the end of the major period of cerebellar histogenesis (P14), lose expression of the PC marker calbindin. These results suggest that the removal of ectopically located neurons may be a previously unrecognized function of developmental PCD.