Abstract
Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMRP protein in the nervous system like autistic behavior and mild-to-severe intellectual disability. Fragile-X (FraX) individuals also display cellular and morphological traits including branched dendritic spines, large ears, and macroorchidism. The dFmr1 gene is the Drosophila ortholog of the human Fmr1 gene. dFmr1 mutant flies exhibit synaptic abnormalities, behavioral defects as well as an altered germline development, resembling the phenotypes observed in FraX patients. Therefore, Drosophila melanogaster is considered a good model to study the physiopathological mechanisms underlying the Fragile-X syndrome. In this review, we explore how the multifaceted roles of the FMRP protein have been addressed in the Drosophila model and how the gained knowledge may open novel perspectives for understanding the molecular defects causing the disease and for identifying novel therapeutical targets.
Highlights
Fragile-X syndrome (FXS, MIM300624) is the most common form of mental retardation in the human population
DFmr1 is involved in the piRNA pathway in the Drosophila gonads as well as in the DNA damage response in Drosophila and mouse (Zhang et al, 2012; Alpatov et al, 2014; Bozzetti et al, 2015) These findings provide a direct link between dFmr1/FMRP and genome instability, which may represent the common denominator for the multiple phenotypes described in the Fragile-X syndrome and in animal models for the disease
A growing number of studies report the identification of piRNAs, piRNA-related proteins, and piRNA-mediated transposition as key factors ensuring heterogeneity in mammalian neurons
Summary
Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMRP protein in the nervous system like autistic behavior and mild-to-severe intellectual disability. The dFmr gene is the Drosophila ortholog of the human Fmr gene. DFmr mutant flies exhibit synaptic abnormalities, behavioral defects as well as an altered germline development, resembling the phenotypes observed in FraX patients. We explore how the multifaceted roles of the FMRP protein have been addressed in the Drosophila model and how the gained knowledge may open novel perspectives for understanding the molecular defects causing the disease and for identifying novel therapeutical targets
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