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Koch M, Nicolas M, Zschaetzsch M, et al. A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury. Front Cell Neurosci. 2018;11:416doi: 10.3389/fncel.2017.00416.
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. Frontiers in cellular neuroscience, 11416. https://doi.org/10.3389/fncel.2017.00416
Koch, Marta, et al. "A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury." Frontiers in cellular neuroscience vol. 11 (2017): 416. doi: https://doi.org/10.3389/fncel.2017.00416
Koch M, Nicolas M, Zschaetzsch M, de Geest N, Claeys A, Yan J, Morgan MJ, Erfurth ML, Holt M, Schmucker D, Hassan BA. A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury. Front Cell Neurosci. 2018 Feb 08;11:416. doi: 10.3389/fncel.2017.00416. eCollection 2017. PMID: 29472843; PMCID: PMC5809495.
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Front Cell Neurosci. 2018 Feb 08;11:416. doi: 10.3389/fncel.2017.00416. eCollection 2017.

A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury.

Frontiers in cellular neuroscience

Marta Koch, Maya Nicolas, Marlen Zschaetzsch, Natalie de Geest, Annelies Claeys, Jiekun Yan, Matthew J Morgan, Maria-Luise Erfurth, Matthew Holt, Dietmar Schmucker, Bassem A Hassan

Affiliations

  1. Laboratory of Neurogenetics, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium.
  2. Center for Human Genetics, University of Leuven School of Medicine, KU Leuven, Leuven, Belgium.
  3. Neuronal Wiring Lab, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium.
  4. Laboratory of Glia Biology, Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium.
  5. Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut du Cerveau et de la Moelle Epinière, Hôpital Pitié-Salpêtrière, UPMC, Sorbonne Universités, Paris, France.

PMID: 29472843 PMCID: PMC5809495 DOI: 10.3389/fncel.2017.00416

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.

Keywords: Central nervous system; Drosophila melanogaster; axonal growth; axonal injury; post-transcriptional reguylatiopn

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