title: FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage.
abstract: The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Naruse
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Shibasaki
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan. Electronic address: yasukiishizaki@gunma-u.ac.jp.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ishizaki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002531:Cerebellum / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology*; D015398:Signal Transduction
chemical_list: D018960:Hyaluronan Receptors; D016222:Fibroblast Growth Factor 2
keywords: CD44; Cerebellum; Development; FGF-2; Neural stem cell; Oligodendrocyte