Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.05.017 Byline: Masae Naruse (a)(b), Eiko Nakahira (c), Takaki Miyata (d), Seiji Hitoshi (a)(b), Kazuhiro Ikenaka (a)(b), Rashmi Bansal (e) Keywords: Fibroblast growth factor-2; Oligodendrocyte; Olig2; PDGFR[alpha]; Sonic hedgehog; Nkx2.1; Dlx2; Patched1; Myelin Abstract: During embryonic development, oligodendrocyte progenitors (OLPs) originate from the ventral forebrain under the regulation of Sonic hedgehog (Shh). Shh controls the expression of transcription factor Olig2, which is strongly implicated in OLP generation. Studies of mice deficient in Shh expression suggest, however, that an alternative pathway for OLP generation may exist. The generation of OLPs in dorsal forebrain has been suggested since treatment of dorsal-neural progenitor cells in culture with fibroblast growth factor (FGF-2) results in OLP induction. To ask if dorsal induction of OLPs in embryonic forebrain can occur in vivo and if FGF-2 could initiate an alternative pathway of regulation, we used in utero microinjection of FGF-2 into the lateral ventricles of mouse fetal forebrain. A single injection of FGF-2 at E13.5 resulted in the expression of the OLP markers Olig2 and PDGFR[alpha] mRNA in dorsal forebrain ventricular and intermediate zones. However, FGF-2 did not induce dorsal expression of Shh, Patched1 or Nkx2.1, and co-injection of FGF-2 and a Shh inhibitor did not attenuate the induction of Olig2 and PDGFR[alpha], suggesting that Shh signaling was not involved in this FGF-2-mediated dorsal induction. These results demonstrate that the dorsal embryonic forebrain in vivo has the potential to generate OLPs in the presence of normal positional cues and that this can be driven by FGF-2 independent of Shh signaling. Author Affiliation: (a) Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies, Hayama, Miura, Kanagawa 240-0193, Japan (b) Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan (c) Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan (d) Department of Anatomy and Cell Biology, Graduate School of Medicine, Nagoya University, 65 tsurumai Shouwaku, Nagoya 466-8550, Japan (e) Department of Neuroscience, University of Connecticut Medical School, 263 Farmington Avenue, Farmington, CT 06030-3401, USA Article History: Received 18 November 2005; Revised 11 May 2006; Accepted 15 May 2006