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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology
  • Central Nervous System / cytology
  • Central Nervous System / embryology
  • Chick Embryo
  • Gene Expression Regulation, Developmental / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Membrane Proteins / physiology
  • Mice
  • NFI Transcription Factors / physiology*
  • Neuroglia / cytology*
  • Neuroglia / physiology
  • Organogenesis / physiology
  • SOX9 Transcription Factor / physiology*
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Transcription, Genetic


  • Apcdd1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NFI Transcription Factors
  • Nfia protein, mouse
  • SOX9 Transcription Factor
  • Sox9 protein, mouse