Disruption of CK2β in Embryonic Neural Stem Cells Compromises Proliferation and Oligodendrogenesis in the Mouse Telencephalon
Disruption of CK2β in Embryonic Neural Stem Cells Compromises Proliferation and Oligodendrogenesis in the Mouse Telencephalon
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DOI：
10.1128/mcb.01566-09
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发表时间：
2010-06-01
影响因子：
5.3
通讯作者：
Buchou, Thierry
中科院分区：
文献类型：
--
作者：
Huillard, Emmanuelle;Ziercher, Lea;Buchou, Thierry
控制神经干/祖细胞（NSC）增殖和分化的遗传程序依赖于细胞外信号和转录因子网络，其可以通过磷酸化进行后期调节。然而，很少有人知道激酶依赖的途径调节神经干细胞的维护和少突胶质细胞的发展。我们使用条件性敲除方法靶向胚胎神经祖细胞中蛋白激酶酪蛋白激酶2（CK 2 β）的鼠调节亚基（β）。CK 2 β的缺失导致胚胎神经干细胞增殖和分化的缺陷。我们建立CK 2 β作为一个关键的积极调节少突胶质细胞前体细胞（OPCs）的发展，在体内和体外。我们发现，CK 2 β直接与碱性螺旋-环-螺旋（bHLH）转录因子Olig 2相互作用，Olig 2是OPC发育的关键调节因子，并激活其富含丝氨酸-苏氨酸（STR）结构域的CK 2依赖性磷酸化。最后，我们揭示了CK 2靶向的STR结构域是Olig 2的少突胶质功能所需的。这些研究结果表明，CK 2可能控制少突分化，部分，通过调节谱系特异性转录因子Olig 2的活性。因此，CK 2 β似乎在中枢神经系统发育中发挥重要且无补偿的作用。
Genetic programs that govern neural stem/progenitor cell (NSC) proliferation and differentiation are dependent on extracellular cues and a network of transcription factors, which can be regulated posttranslationally by phosphorylation. However, little is known about the kinase-dependent pathways regulating NSC maintenance and oligodendrocyte development. We used a conditional knockout approach to target the murine regulatory subunit (beta) of protein kinase casein kinase 2 (CK2 beta) in embryonic neural progenitors. Loss of CK2 beta leads to defects in proliferation and differentiation of embryonic NSCs. We establish CK2 beta as a key positive regulator for the development of oligodendrocyte precursor cells (OPCs), both in vivo and in vitro. We show that CK2 beta directly interacts with the basic helix-loop-helix (bHLH) transcription factor Olig2, a critical modulator of OPC development, and activates the CK2-dependent phosphorylation of its serine-threonine-rich (STR) domain. Finally, we reveal that the CK2-targeted STR domain is required for the oligodendroglial function of Olig2. These findings suggest that CK2 may control oligodendrogenesis, in part, by regulating the activity of the lineage-specific transcription factor Olig2. Thus, CK2 beta appears to play an essential and uncompensated role in central nervous system development.