BMP signaling mutant mice exhibit glial cell maturation defects

Mol Cell Neurosci. 2007 May;35(1):171-82. doi: 10.1016/j.mcn.2007.02.012. Epub 2007 Feb 23.

Abstract

Bone morphogenetic proteins have been implicated in the development of oligodendrocytes and astrocytes, however, a role for endogenous BMP signaling in glial development has not been demonstrated in a genetic model. Using mice in which signaling via type I BMP receptors Bmpr1a and Bmpr1b have been inactivated in the neural tube, we demonstrate that BMP signaling contributes to the maturation of glial cells in vivo. At P0, mutant mice exhibited a 25-40% decrease in GFAP+ or S100beta+ astrocytes in the cervical spinal cord. The number of oligodendrocyte precursors and the timing of their emergence was unchanged in the mutant mice compared to the normals, however myelin protein expression and mature oligodendrocyte numbers were significantly reduced. These data indicate that BMP signaling promotes the generation of astrocytes and mature, myelinating oligodendrocytes in vivo but does not affect oligodendrocyte precursor development, thus suggesting tight regulation of BMP signaling to ensure proper gliogenesis.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Bone Morphogenetic Protein 1
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Death / physiology
  • Cell Division / physiology
  • Cell Lineage / physiology
  • Cervical Vertebrae
  • Female
  • Male
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Myelin Proteins / metabolism
  • Neural Tube Defects / metabolism
  • Neural Tube Defects / pathology*
  • Oligodendroglia / metabolism*
  • Oligodendroglia / pathology
  • Pregnancy
  • Signal Transduction / physiology*
  • Spinal Cord / abnormalities
  • Spinal Cord / metabolism
  • Spinal Cord / pathology*
  • Stem Cells / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Myelin Proteins
  • Metalloendopeptidases
  • Bmp1 protein, mouse
  • Bone Morphogenetic Protein 1