Nuclear factor-kappaB regulates multiple steps of gliogenesis in the developing murine cerebral cortex

Glia. 2018 Dec;66(12):2659-2672. doi: 10.1002/glia.23518. Epub 2018 Oct 19.

Abstract

Nuclear factor-kappaB (NF-κB) is activated in neural progenitor cells in the developing murine cerebral cortex during the neurogenic phase, when it acts to prevent premature neuronal differentiation. Here we show that NF-κB activation continues in mouse neocortical neural progenitor cells during the neurogenic-to-gliogenic switch. Blockade of endogenous NF-κB activity during neocortical gliogenesis leads to the formation of supernumerary committed gliogenic progenitors and premature glial cell differentiation. Conversely, forced NF-κB activation during the neocortical neurogenic-to-gliogenic transition causes delayed gliogenic commitment and decreased astroglial gene expression. NF-κB activation continues in neocortical gliogenic progenitors following commitment and is important to inhibit the differentiation of oligodendrocyte precursor cells and to maintain persistent expression of glial fibrillary acidic protein in maturing astrocytes. These results reveal a number of previously uncharacterized roles for NF-κB during different phases of neocortical gliogenesis and identify NF-κB as an inhibitor of early oligodendrocyte development in the cerebral cortex.

Keywords: astrocyte; cerebral cortex; gliogenesis; nuclear factor-kappaB; oligodendrocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / embryology
  • Cerebral Cortex* / growth & development
  • Cerebral Ventricles / cytology
  • Cerebral Ventricles / embryology
  • Cerebral Ventricles / growth & development
  • Ciliary Neurotrophic Factor / pharmacology
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology
  • Neurogenesis / genetics*
  • Neuroglia / physiology*

Substances

  • Ciliary Neurotrophic Factor
  • Glial Fibrillary Acidic Protein
  • Ki-67 Antigen
  • NF-kappa B
  • Nerve Tissue Proteins
  • I-kappa B Kinase