Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice

Mei Xin, Tao Yue, Zhenyi Ma, Fen Fen Wu, Alexander Gow, Q. Richard Lu

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

Myelin-forming oligodendrocytes facilitate saltatory nerve conduction and support neuronal functions in the mammalian CNS. Although the processes of oligodendrogliogenesis and differentiation from neural progenitor cells have come to light in recent years, the molecular mechanisms underlying oligodendrocyte myelinogenesis are poorly defined. Herein, we demonstrate the pivotal role of the basic helix-loop-helix transcription factor, Olig1, in oligodendrocyte myelinogenesis in brain development. Mice lacking a functional Olig1 gene develop severe neurological deficits and die in the third postnatal week. In the brains of these mice, expression of myelin-specific genes is abolished, whereas the formation of oligodendrocyte progenitors is not affected. Furthermore, multilamellar wrapping of myelin membranes around axons does not occur, despite recognition and contact of axons by oligodendrocytes, and Olig1-null mice develop widespread progressive axonal degeneration and gliosis. In contrast, myelin sheaths are formed in the spinal cord, although the extent of myelination is severely reduced. At the molecular level, we find that Olig1 regulates transcription of the major myelin-specific genes, Mbp, Plp1, and Mag, and suppresses expression of a major astrocyte-specific gene, Gfap. Together, our data indicate that Olig1 is a central regulator of oligodendrocyte myelinogenesis in brain and that axonal recognition and myelination by oligodendrocytes are separable processes.

Original languageEnglish (US)
Pages (from-to)1354-1365
Number of pages12
JournalJournal of Neuroscience
Volume25
Issue number6
DOIs
StatePublished - Feb 9 2005

Keywords

  • Axonal integrity
  • Gene knock-out
  • Mouse models
  • Myelin assembly
  • Olig genes
  • Oligodendrocytes

ASJC Scopus subject areas

  • Neuroscience(all)

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