| First Author | Michaelson MD | Year | 1996 |
| Journal | Development | Volume | 122 |
| Issue | 9 | Pages | 2661-72 |
| PubMed ID | 8787741 | Mgi Jnum | J:35818 |
| Mgi Id | MGI:83262 | Doi | 10.1242/dev.122.9.2661 |
| Citation | Michaelson MD, et al. (1996) CSF-1 deficiency in mice results in abnormal brain development. Development 122(9):2661-72 |
| abstractText | 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. |
