TY - JOUR T1 - Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury JF - bioRxiv DO - 10.1101/148239 SP - 148239 AU - Marta Koch AU - Maya Nicolas AU - Marlen Zschaetzsch AU - Natalie de Geest AU - Annelies Claeys AU - Jiekun Yan AU - Matthew Morgan AU - Marie-Luise Erfurth AU - Matthew Holt AU - Dietmar Schmucker AU - Bassem A Hassan Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/09/148239.abstract N2 - Injury to the adult central nervous systems (CNS) results in severe long-term disability because damaged CNS connections rarely regenerate. Although several axon regeneration regulators have been proposed, intrinsic regenerative mechanisms remain largely unexplored. Here, we use a Drosophila CNS injury model to identify a novel pro-regeneration signaling pathway. We conducted a genetic screen of approximately three hundred candidate genes and identified three strong inducers of axonal growth and regeneration: the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3’-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism. ER -