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Potent activation of FGF-2 IRES-dependent mechanism of translation during brain development
Authors:Audigier Sylvie  Guiramand Janique  Prado-Lourenco Leonel  Conte Caroline  Gonzalez-Herrera Irma Gabriela  Cohen-Solal Catherine  Récasens Max  Prats Anne-Catherine
Institution:Sylvie Audigier, Janique Guiramand, Leonel Prado-Lourenco, Caroline Conte, Irma Gabriela Gonzalez-Herrera, Catherine Cohen-Solal, Max Récasens, and Anne-Catherine Prats
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.
Keywords:FGF-2  protein synthesis  IRES  development  brain  neuron
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