Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury
Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury
Abstract 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.
Claeys Annelies、Hassan Bassem A、Morgan Matthew、Nicolas Maya、Zschaetzsch Marlen、de Geest Natalie、Erfurth Marie-Luise、Schmucker Dietmar、Yan Jiekun、Holt Matthew、Koch Marta
VIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of MedicineVIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of Medicine||Institut du Cerveau et de la Moelle Epini¨¨re (ICM)VIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of MedicineVIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of MedicineVIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of MedicineVIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of MedicineVesalius Research Center||Department of Oncology, University of Leuven School of MedicineVesalius Research Center||Department of Oncology, University of Leuven School of MedicineVIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of MedicineCenter for Human Genetics, University of Leuven School of Medicine||Laboratory of Glia Biology, VIB Center for the Biology of DiseaseVIB Center for the Biology of Disease||Center for Human Genetics, University of Leuven School of Medicine
分子生物学遗传学细胞生物学
Claeys Annelies,Hassan Bassem A,Morgan Matthew,Nicolas Maya,Zschaetzsch Marlen,de Geest Natalie,Erfurth Marie-Luise,Schmucker Dietmar,Yan Jiekun,Holt Matthew,Koch Marta.Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/148239.点此复制
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