RESUMO
We used loss-of-function analysis to determine the role of fibroblast growth factor receptor 2 (FGFR2) in telencephalic progenitors, and also to examine interactions between FGFR and Notch signaling. While the telencephalon of FGFR2 mutants appears grossly normal, mutant telencephalic progenitors exhibit altered proliferative behavior in vivo and in vitro. Based upon our prior finding that Notch1 activation increased neurosphere frequency in FGF2, we tested whether this effect is mediated by FGFR1 or FGFR2. We found that Notch1 activation increased neurosphere frequency in cells mutant for either FGFR1 or FGFR2, but had no effect on the reduced size of neurospheres mutant for those receptors. Additional analyses revealed biochemical changes in the adult neocortex mutant for the IIIc isoform of FGFR2, and essential roles for FGFR2 in nasopharynx, eyelid, and cornea development.
Assuntos
Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Células-Tronco/fisiologia , Telencéfalo , Animais , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Córnea/crescimento & desenvolvimento , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/fisiologia , Pálpebras/crescimento & desenvolvimento , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Camundongos , Camundongos Knockout , Nasofaringe/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Notch1/genética , Receptor Notch1/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/citologia , Telencéfalo/citologia , Telencéfalo/metabolismoRESUMO
Cells with radial morphology in the developing brain were first identified more than 100 years ago. These cells, later termed radial glia, have been studied primarily as migratory scaffolds and glial progenitors. However, it has become increasingly clear, on the basis of in vitro studies and more recent in vivo fate mapping experiments, that radial glia also generate neurons during embryonic development. Now the challenge will be to understand the signaling events that regulate the spatial and temporal heterogeneity of these cells and their developmental potential. Recent work has identified the Notch, ErbB, and fibroblast growth factor signaling pathways as central to the regulation of radial 'glial' progenitors.