Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.06.001 Byline: Katsuhiko Ono (a)(b), Hirohide Takebayashi (a)(b), Kazuyo Ikeda (a)(c), Miki Furusho (a)(b), Takumi Nishizawa (a)(b), Keisuke Watanabe (a)(b), Kazuhiro Ikenaka (a)(b) Keywords: Cre/loxP; Tamoxifen; Astrocyte; Oligodendrocyte; GABAergic neuron; Glutamatergic neuron Abstract: Olig2 is a basic helix-loop-helix transcription factor essential for oligodendrocyte and motoneuron development in the spinal cord. Olig2-positive (Olig2+) cells in the ventricular zone of the ventral telencephalon have been shown to differentiate into GABAergic and cholinergic neurons. However, the fate of Olig2 lineage cells in the postnatal forebrain has not been fully described and Olig2 may regulate the development of both astrocytes and oligodendrocytes. Here, we examined the fate of embryonic Olig2+ progenitors using a tamoxifen-inducible Cre/loxP system. Using long-term lineage tracing, Olig2+ cells in the early fetal stage primarily differentiated into GABAergic neurons in the adult telencephalon, while those in later stages gave rise to macroglial cells, both astrocytes and oligodendrocytes. Olig2+ progenitors in the diencephalon developed into oligodendrocytes, as observed in the spinal cord, and a fraction developed into glutamatergic neurons. Olig2 lineage oligodendrocytes tended to form clusters, probably due to local proliferation at the site of terminal differentiation. In spite of the abundance of Olig2 lineage GABAergic neurons in the normal neocortex, GABAergic neurons seemed to develop at normal density in the Olig2 deficient mouse. Thus, Olig2 is dispensable for GABAergic neuron specification. In contrast, at the late fetal stage in the Olig2 deficient mouse, astrocyte development was retarded in the dorsal neocortex, but not in the basal forebrain. Olig2 functions, therefore, in gliogenesis in the dorsal pallium. Short-term lineage tracing experiments revealed that the majority of late Olig2+ cells were not direct descendants of early Olig2+ progenitors in the fetal forebrain. These observations indicate that embryonic Olig2+ progenitor cells change their differentiative properties during development, and also that Olig2 plays a role in astrocyte development in a region-specific manner. Author Affiliation: (a) Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan (b) Department of Physiological Sciences, School of Life Science, The Graduate University of Advanced Studies (Sokendai), Miki-cho, Kanagawa 240-0193, Japan (c) Third Department of Internal Medicine, Kagawa University School of Medicine, Kagawa 761-0793, Japan Article History: Received 24 October 2007; Revised 19 May 2008; Accepted 2 June 2008

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