Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2.
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 PDGFRalpha 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 PDGFRalpha, 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.
Naruse
Masae
M
Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies, Hayama, Miura, Kanagawa 240-0193, Japan.
Nakahira
Eiko
E
Miyata
Takaki
T
Hitoshi
Seiji
S
Ikenaka
Kazuhiro
K
Bansal
Rashmi
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004627:Embryonic Induction / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D011956:Receptors, Cell Surface; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; C088334:Distal-less homeobox proteins; C000614414:Nkx2-1 protein, mouse; C512773:Olig2 protein, mouse; C000606240:Ptch1 protein, mouse; C465570:Shh protein, mouse