PDGF A chain homodimers drive proliferation of bipotential (O-2A) glial progenitor cells in the developing rat optic nerve

EMBO J. 1989 Apr;8(4):1049-56.

Abstract

The bipotential glial progenitor cells (O-2A progenitors), which during development of the rat optic nerve give rise to oligodendrocytes and type 2 astrocytes, are stimulated to divide in culture by platelet-derived growth factor (PDGF), and there is evidence that PDGF is important for development of the O-2A cell lineage in vivo. We have visualized PDGF mRNA in the rat optic nerve by in situ hybridization, and its spatial distribution is compatible with the idea that type 1 astrocytes are the major source of PDGF in the nerve. We can detect mRNA encoding the A chain, but not the B chain of PDGF in the brain and optic nerve, suggesting that the major form of PDGF in the central nervous system is a homodimer of A chains (PDGF-AA). PDGF-AA is a more potent mitogen for O-2A progenitor cells than is PDGF-BB, while the reverse is true for human or rat fibroblasts. Fibroblasts display two types of PDGF receptors, type A receptors which bind to all three dimeric isoforms of PDGF, and type B receptors which bind PDGF-BB and PDGF-AB, but have low affinity for PDGF-AA. Our results suggest that O-2A progenitor cells possess predominantly type A receptors, and proliferate during development in response to PDGF-AA secreted by type 1 astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Mitogens
  • Neuroglia / cytology
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Optic Nerve / cytology
  • Optic Nerve / drug effects*
  • Optic Nerve / growth & development
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / pharmacology*
  • Platelet-Derived Growth Factor / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Cell Surface / metabolism
  • Receptors, Platelet-Derived Growth Factor
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Mitogens
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Platelet-Derived Growth Factor