RT Journal Article SR Electronic T1 Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury JF bioRxiv FD Cold Spring Harbor Laboratory SP 148239 DO 10.1101/148239 A1 Marta Koch A1 Maya Nicolas A1 Marlen Zschaetzsch A1 Natalie de Geest A1 Annelies Claeys A1 Jiekun Yan A1 Matthew Morgan A1 Marie-Luise Erfurth A1 Matthew Holt A1 Dietmar Schmucker A1 Bassem A Hassan YR 2017 UL http://biorxiv.org/content/early/2017/06/09/148239.abstract AB 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.