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Koch, M., Nicolas, M., Zschaetzsch, M., de Geest, N., Claeys, A., Yan, J., Morgan, M.J., Erfurth, M.L., Holt, M., Schmucker, D., Hassan, B.A. (2017). A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury.  Front. Cell. Neurosci. 11(): 416.
FlyBase ID
FBrf0238178
Publication Type
Research paper
Abstract
Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis 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.
PubMed ID
PubMed Central ID
PMC5809495 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Front. Cell. Neurosci.
    Title
    Frontiers in cellular neuroscience
    ISBN/ISSN
    1662-5102
    Data From Reference
    Genes (10)
    Cell Lines (1)