Sox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis.

Sox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis.
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DOI:
10.1016/j.neuron.2012.01.024
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发表时间:
2012-04-12
期刊:
影响因子:
16.2
通讯作者:
Deneen B
Deneen B
中科院分区:
医学1区
文献类型:
--
作者:
Kang P;Lee HK;Glasgow SM;Finley M;Donti T;Gaber ZB;Graham BH;Foster AE;Novitch BG;Gronostajski RM;Deneen B

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在谱系发育过程中起作用的转录级联是控制细胞分化的基本机制。在发育中的中枢神经系统(CNS)中,这些机制在神经发生过程中得到了很好的表征,但在神经干细胞向胶质细胞谱系的定向分化过程中仍然定义不清。NFIA是一种转录因子,在胶质细胞生成的发病中起着至关重要的作用,我们发现,其诱导受转录因子Sox 9的调节,这种关系介导胶质细胞生成的启动。随后,Sox 9和NFIA形成复合物,共同调节胶质细胞起始后诱导的一组基因。功能研究表明,这些基因的一个子集,Apcdd1和Mmd2,执行关键的迁移和代谢的作用,在星形胶质细胞的形成,分别。总之,这些研究描绘了一个转录调控级联反应,在胶质细胞生成的启动过程中运作,并确定了一组独特的基因,调节发育过程中的星形胶质细胞前体生理学的关键方面。
Transcriptional cascades that operate over the course of lineage development are fundamental mechanisms that control cellular differentiation. In the developing central nervous system (CNS), these mechanisms are well characterized during neurogenesis, but remain poorly defined during neural stem cell commitment to the glial lineage. NFIA is a transcription factor that plays a crucial role in the onset of gliogenesis; we found that its induction is regulated by the transcription factor Sox9 and that this relationship mediates the initiation of gliogenesis. Subsequently, Sox9 and NFIA form a complex and coregulate a set of genes induced after glial initiation. Functional studies revealed that a subset of these genes, Apcdd1 and Mmd2, perform key migratory and metabolic roles during astro-gliogenesis, respectively. In sum, these studies delineate a transcriptional regulatory cascade that operates during the initiation of gliogenesis and identifies a unique set of genes that regulate key aspects of astro-glial precursor physiology during development.
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