Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury

Koch, M.; Nicolas, M.; Zschaetzsch, M.; de Geest, N.; Claeys, A.; Yan, J.; Morgan, M.; Erfurth, M.-L.; Holt, M.; Schmucker, D.; Hassan, B.

doi:10.1101/148239

bioRxiv · 10.1101/148239

Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury

Koch, M.·Nicolas, M.·Zschaetzsch, M.·de Geest, N.·Claeys, A.·Yan, J.·Morgan, M.·Erfurth, M.-L.·Holt, M.·Schmucker, D.·Hassan, B.

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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.

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Koch, M., Nicolas, M., Zschaetzsch, M., de Geest, N., Claeys, A., Yan, J., Morgan, M., Erfurth, M.-L., Holt, M., Schmucker, D., Hassan, B.. 2017-06-09. Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury. https://doi.org/10.1101/148239

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