Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Neuron. 2012 Apr 12;74(1):79-94. doi: 10.1016/j.neuron.2012.01.024.
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.
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。在中枢神经系统（CNS）的发育过程中，这些机制在神经发生过程中得到了很好的描述，但在神经干细胞向神经胶质谱系分化时仍然定义不明确。NFIA 是一种转录因子，在神经胶质发生的开始中起着至关重要的作用；我们发现它的诱导受到转录因子 Sox9 的调节，这种关系介导了神经胶质发生的开始。随后，Sox9 和 NFIA 形成一个复合物，并共同调节一组在神经胶质起始后诱导的基因。功能研究表明，这些基因中的一部分，Apcdd1 和 Mmd2，分别在星形胶质发生过程中发挥关键的迁移和代谢作用。总之，这些研究描绘了一个在神经胶质发生开始时起作用的转录调控级联，并确定了一组独特的基因，它们在发育过程中调节星形胶质前体生理学的关键方面。
