title: Potent activation of FGF-2 IRES-dependent mechanism of translation during brain development.
abstract: Fibroblast growth factor-2 (FGF-2) plays a fundamental role in brain functions. This role may be partly achieved through the control of its expression at the translational level via an internal ribosome entry site (IRES)-dependent mechanism. Transgenic mice expressing a bicistronic mRNA allowed us to study in vivo and ex vivo where this translational mechanism operates. Along brain development, we identified a stringent spatiotemporal regulation of FGF-2 IRES activity showing a peak at post-natal day 7 in most brain regions, which is concomitant with neuronal maturation. At adult age, this activity remained relatively high in forebrain regions. By the enrichment of this activity in forebrain synaptoneurosomes and by the use of primary cultures of cortical neurons or cocultures with astrocytes, we showed that this activity is indeed localized in neurons, is dependent on their maturation, and correlates with endogenous FGF-2 protein expression. In addition, this activity was regulated by astrocyte factors, including FGF-2, and spontaneous electrical activity. Thus, neuronal IRES-driven translation of the FGF-2 mRNA may be involved in synapse formation and maturation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U858, Toulouse, France. sylvie.audigier@inserm.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Audigier
authors.forename: Janique
authors.initials: J
authors.lastname: Guiramand
authors.forename: Leonel
authors.initials: L
authors.lastname: Prado-Lourenco
authors.forename: Caroline
authors.initials: C
authors.lastname: Conte
authors.forename: Irma Gabriela
authors.initials: IG
authors.lastname: Gonzalez-Herrera
authors.forename: Catherine
authors.initials: C
authors.lastname: Cohen-Solal
authors.forename: Max
authors.initials: M
authors.lastname: Récasens
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Prats
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D054351:Electrical Synapses / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017470:Receptors, Glutamate / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D016222:Fibroblast Growth Factor 2