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

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

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=11

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00416

DOI=10.3389/fncel.2017.00416

ISSN=1662-5102

ABSTRACT=<p>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.</p>