Open Close
Russo, A., DiAntonio, A. (2019). Wnd/DLK Is a Critical Target of FMRP Responsible for Neurodevelopmental and Behavior Defects in the Drosophila Model of Fragile X Syndrome.  Cell Rep. 28(10): 2581--2593.e5.
FlyBase ID
Publication Type
Research paper

Fragile X syndrome (FXS) is the leading heritable cause of intellectual disability and commonly co-occurs with autism spectrum disorder. Silencing of the Fmr1 gene leads to the absence of the protein product, fragile X mental retardation protein (FMRP), which represses translation of many target mRNAs. Excess translation of these targets is one cause of neuronal dysfunction in FXS. Utilizing the Drosophila model of FXS, we identified the mitogen-activated protein kinase kinase kinase (MAP3K) Wallenda/dual leucine zipper kinase (DLK) as a critical target of FMRP. dFMRP binds Wallenda mRNA and is required to limit Wallenda protein levels. In dFmr1 mutants, Wallenda signaling drives defects in synaptic development, neuronal morphology, and behavior. Pharmacological inhibition of Wallenda in larvae suppresses dFmr1 neurodevelopmental phenotypes, while adult administration prevents dFmr1 behavioral defects. We propose that in dFmr1 mutants chronic Wallenda/DLK signaling disrupts nervous system development and function and that inhibition of this kinase cascade might be a candidate therapeutic intervention for the treatment of FXS.

PubMed ID
PubMed Central ID
PMC6746345 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Cell Rep.
    Cell reports
    Data From Reference
    Aberrations (1)
    Alleles (15)
    Genes (7)
    Human Disease Models (1)
    Physical Interactions (2)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (7)