differential fibroblast growth factor 8 (fgf8)-mediated autoregulation of its cognate receptors, fgfr1 and fgfr3, in neuronal cell lines微分纤维母细胞生长因子8(fgf8)介导的自动调整它的同源受体,fgfr1、fgfr3在神经细胞系.pdfVIP

Differential Fibroblast Growth Factor 8 (FGF8)-Mediated Autoregulation of Its Cognate Receptors, Fgfr1 and Fgfr3, in Neuronal Cell Lines 1 2 2 1 Natasha N. Mott , Wilson C. J. Chung , Pei-San Tsai , Toni R. Pak * 1 Department of Cell and Molecular Physiology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America, 2 Department of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado, United States of America Abstract Fibroblast growth factors (FGFs) mediate a vast range of CNS developmental processes including neural induction, proliferation, migration, and cell survival. Despite the critical role of FGF signaling for normal CNS development, few reports describe the mechanisms that regulate FGF receptor gene expression in the brain. We tested whether FGF8 could autoregulate two of its cognate receptors, Fgfr1 and Fgfr3, in three murine cell lines with different lineages: fibroblast-derived cells (3T3 cells), neuronal cells derived from hippocampus (HT-22 cells), and neuroendocrine cells derived from hypothalamic gonadotropin-releasing hormone (GnRH) neurons (GT1-7 cells). GnRH is produced by neurons in the hypothalamus and is absolutely required for reproductive competence in vertebrate animals. Several lines of evidence strongly suggest that Fgf8 is critical for normal development of the GnRH system, therefore, the GT1-7 cells provided us with an additional endpoint, Gnrh gene expression and promoter activity, to assess potential downstream consequences of FGF8-induced modulation of FGF receptor levels. Results from this study suggest that the autoregulation of its cognate receptor represents a common downstr