Synergistic induction of astrocytic differentiation by factors secreted from meninges in the mouse developing brain

FEBS Lett. 2017 Nov;591(22):3709-3720. doi: 10.1002/1873-3468.12881. Epub 2017 Oct 31.

Abstract

Astrocytes, which support diverse neuronal functions, are generated from multipotent neural stem/precursor cells (NS/PCs) during brain development. Although many astrocyte-inducing factors have been identified and studied in vitro, the regions and/or cells that produce these factors in the developing brain remain elusive. Here, we show that meninges-produced factors induce astrocytic differentiation of NS/PCs. Consistent with the timing when astrocytic differentiation of NS/PCs increases, expression of astrocyte-inducing factors is upregulated. Meningeal secretion-mimicking combinatorial treatment of NS/PCs with bone morphogenetic protein 4, retinoic acid and leukemia inhibitory factor synergistically activate the promoter of a typical astrocytic marker, glial fibrillary acidic protein. Taken together, our data suggest that meninges play an important role in astrocytic differentiation of NS/PCs in the developing brain.

Keywords: astrocyte differentiation; meninges; neural stem/precursor cells.

Publication types

  • Letter

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Bone Morphogenetic Protein 4 / metabolism
  • Brain / cytology
  • Brain / growth & development*
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology
  • Glial Fibrillary Acidic Protein / genetics*
  • Leukemia Inhibitory Factor / metabolism
  • Meninges / cytology
  • Meninges / metabolism*
  • Mice
  • Mouse Embryonic Stem Cells / cytology*
  • Neurogenesis
  • Tretinoin / metabolism

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Culture Media, Conditioned
  • Glial Fibrillary Acidic Protein
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • glial fibrillary astrocytic protein, mouse
  • Tretinoin