Early postnatal in vivo gliogenesis from nestin-lineage progenitors requires cdk5.
Early postnatal in vivo gliogenesis from nestin-lineage progenitors requires cdk5.
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DOI：
10.1371/journal.pone.0072819
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Eisch AJ
中科院分区：
文献类型：
--
作者：
Petrik D;Yun S;Latchney SE;Kamrudin S;LeBlanc JA;Bibb JA;Eisch AJ
出生后早期是大脑发育的一个独特时期，因为神经发生的数量减少与胶质细胞生成的浪潮共存。了解出生后早期胶质细胞发生的分子调控可能为正常和病理性胚胎脑个体发育提供线索，特别是在星形胶质细胞和少突胶质细胞的发育方面。细胞周期蛋白依赖性激酶5（Cdk 5）有助于胚胎发育过程中的神经元迁移和细胞周期控制，以及成年期神经元和少突胶质细胞的分化。然而，Cdk 5在出生后时期和离散的祖细胞谱系内的功能是未知的。因此，我们通过在出生后（P）天P2-P4或P7-P9期间给予转基因小鼠（nestin-CreERT 2/R26 R-YFP/CDK 5 flox/flox [iCdk 5]和nestin-CreERT 2/R26 R-YFP/CDK 5 wt/wt [WT]）他莫昔芬，并在P14和P21时定量和表型化重组（YFP+）细胞，选择性地从表达nestin的细胞及其后代中去除Cdk 5。当Cdk 5基因缺失诱导巢蛋白表达细胞及其后代在皮层和海马胶质细胞生成波（P2-P4），显着减少YFP+细胞明显在皮层，胼胝体，海马。表型分析显示皮质减少是由于较少的YFP+星形胶质细胞和少突胶质细胞，在少突胶质细胞中观察到的影响略早于星形胶质细胞。这种对皮质胶质细胞生成的影响伴随着YFP+增殖细胞的减少，但不增加细胞死亡。Cdk 5在胶质细胞生成中的作用似乎特异于出生后早期，因为在出生后后期（P7-P9）诱导重组导致皮质或海马中的YFP+细胞数量没有变化。因此，神经胶质细胞来源于巢蛋白表达细胞和它们的后代需要Cdk 5在出生后早期的适当发展。
The early postnatal period is a unique time of brain development, as diminishing amounts of neurogenesis coexist with waves of gliogenesis. Understanding the molecular regulation of early postnatal gliogenesis may provide clues to normal and pathological embryonic brain ontogeny, particularly in regards to the development of astrocytes and oligodendrocytes. Cyclin dependent kinase 5 (Cdk5) contributes to neuronal migration and cell cycle control during embryogenesis, and to the differentiation of neurons and oligodendrocytes during adulthood. However, Cdk5’s function in the postnatal period and within discrete progenitor lineages is unknown. Therefore, we selectively removed Cdk5 from nestin-expressing cells and their progeny by giving transgenic mice (nestin-CreERT2/R26R-YFP/CDK5flox/flox [iCdk5] and nestin-CreERT2/R26R-YFP/CDK5wt/wt [WT]) tamoxifen during postnatal (P) days P2-P 4 or P7-P 9, and quantified and phenotyped recombined (YFP+) cells at P14 and P21. When Cdk5 gene deletion was induced in nestin-expressing cells and their progeny during the wave of cortical and hippocampal gliogenesis (P2-P4), significantly fewer YFP+ cells were evident in the cortex, corpus callosum, and hippocampus. Phenotypic analysis revealed the cortical decrease was due to fewer YFP+ astrocytes and oligodendrocytes, with a slightly earlier influence seen in oligodendrocytes vs. astrocytes. This effect on cortical gliogenesis was accompanied by a decrease in YFP+ proliferative cells, but not increased cell death. The role of Cdk5 in gliogenesis appeared specific to the early postnatal period, as induction of recombination at a later postnatal period (P7-P9) resulted in no change YFP+ cell number in the cortex or hippocampus. Thus, glial cells that originate from nestin-expressing cells and their progeny require Cdk5 for proper development during the early postnatal period.
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