Fibroblast growth factor signaling is required for the generation of oligodendrocyte progenitors from the embryonic forebrain

Miki Furusho, Yoshimi Kaga, Akihiro Ishii, Jean M. Hébert, Rashmi Bansal

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Abstract

Fibroblast growth factors (FGFs) comprise a family of developmental regulators implicated in a wide variety of neurological functions. FGF receptors 1, 2, and 3 (Fgfrs) are expressed in the embryonic forebrain, including regions overlapping with ventral sites of oligodendrocyte progenitor (OLP) generation. Although FGF signaling is known to influence the proliferation of OLP sin vitro, functions of different Fgfrs in vivo are lacking. Here, we examined single and double mutants with conditional disruption of Fgfrs, specifically in the embryonic forebrain, to investigate the effect of FGF son the generation and proliferation of OLP sin vivo. FGF signaling, through cooperation between Fgfr1 and Fgfr2 but not Fgfr3, is required for the initial generation of OLPs in themouseventral forebrain, with Fgfr1 being a stronger inducer than Fgfr2. Incultures derived from embryonic mutant forebrains or from normal forebrains grown in the presence of Fgfr inhibitor, a strong attenuation of OLP generation was observed, supporting the role of FGF signaling in vivo. Contrary to in vitro findings, Fgfr1 and Fgfr2 signaling is not required for the proliferation of OLPs in vivo. Finally, failure of OLP generation in the Fgfr mutants occurred without loss of sonic hedgehog (Shh) signaling; and pharmacological inhibition of either Fgfr or hedgehog signaling in parallel cultures strongly in habited OLP generation, suggesting that Fgfrscooperate with Shh to generate OLPs. Overall, our results reveal for the first time an essential role of FGF signaling in vivo, where the three Fgfrs differentially control the normal generation of OLPs from the embryonic ventral forebrain.

Original languageEnglish (US)
Pages (from-to)5055-5066
Number of pages12
JournalJournal of Neuroscience
Volume31
Issue number13
DOIs
StatePublished - Mar 30 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

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