CSF-1 deficiency in mice results in abnormal brain development

M. Dror Michaelson, Phyllis L. Bieri, Mark F. Mehler, Hong Xu, Joseph C. Arezzo, Jeffrey W. Pollard, John A. Kessler

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Colony stimulating factor-1 (CSF-1) was initially identified as a growth factor for mononuclear phagocytes. This study examines the role of CSF-1 in the development of the central nervous system (CNS), CSF-1 treatment of neurons cultured from embryonic brain promoted survival and process outgrowth in a dose-dependent manner. By contrast, CSF-1 treatment of neurons cultured from the osteopetrotic (op/op) mouse, a null mutant for CSF-1, promoted significantly less process outgrowth, suggesting that there are neural abnormalities in op/op animals. Nuclease protection assays were used to determine whether CSF-1 and its receptor are expressed at times appropriate to regulate neural development. Both CSF-1 and its receptor are expressed in developing mouse brain, with a unique pattern of CSF-1 mRNA splice variant expression encoding secreted, and not membrane-bound, growth factor. To determine whether brain function is altered by null mutation of CSF-1, op/op mice were examined using electrophysiologic assays. Brainstem auditory and visual evoked potentials were both abnormal in op/op mice. Further, intracortical recordings revealed aberrant neuronal function within visual cortex and alterations in the cortical circuitry that balances excitation and inhibition. Daily CSF-1 injection of postnatal op/op mice largely rescued the abnormal neural phenotype, confirming that the absence of CSF-1 during development is responsible for the abnormalities. The effects of CSF-1 on cultured embryonic neural cells, the developmentally appropriate expression of CSF-1 and its receptor, and the neurological abnormalities in op/op mice suggest a role for CSF-1 in brain development.

Original languageEnglish (US)
Pages (from-to)2661-2672
Number of pages12
JournalDevelopment
Volume122
Issue number9
StatePublished - Oct 10 1996

Keywords

  • Brain
  • CNS development
  • CSF-1
  • Colony stimulating factor
  • Evoked potential
  • Mouse
  • Neurotrophic factor
  • Osteopetrotic
  • op/op mice

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Dror Michaelson, M., Bieri, P. L., Mehler, M. F., Xu, H., Arezzo, J. C., Pollard, J. W., & Kessler, J. A. (1996). CSF-1 deficiency in mice results in abnormal brain development. Development, 122(9), 2661-2672.