ABSTRACT
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.
Subject(s)
Receptor, Fibroblast Growth Factor, Type 2/metabolism , Stem Cells/physiology , Telencephalon , Animals , Biomarkers/metabolism , Cell Proliferation , Cells, Cultured , Cornea/growth & development , Embryo, Mammalian/anatomy & histology , Embryo, Mammalian/physiology , Eyelids/growth & development , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Mice , Mice, Knockout , Nasopharynx/growth & development , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Notch1/genetics , Receptor, Notch1/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Signal Transduction/physiology , Stem Cells/cytology , Telencephalon/cytology , Telencephalon/metabolismABSTRACT
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.
