RRC ID 30457
Author Zhang YQ, Matthies HJ, Mancuso J, Andrews HK, Woodruff E 3rd, Friedman D, Broadie K.
Title The Drosophila fragile X-related gene regulates axoneme differentiation during spermatogenesis.
Journal Dev Biol
Abstract Macroorchidism (i.e., enlarged testicles) and mental retardation are the two hallmark symptoms of Fragile X syndrome (FraX). The disease is caused by loss of fragile X mental retardation protein (FMRP), an RNA-binding translational regulator. We previously established a FraX model in Drosophila, showing that the fly FMRP homologue, dFXR, acts as a negative translational regulator of microtubule-associated Futsch to control stability of the microtubule cytoskeleton during nervous system development. Here, we investigate dFXR function in the testes. Male dfxr null mutants have the enlarged testes characteristic of the disease and are nearly sterile (>90% reduced male fecundity). dFXR protein is highly enriched in Drosophila testes, particularly in spermatogenic cells during the early stages of spermatogenesis. Cytological analyses reveal that spermatogenesis is arrested specifically in late-stage spermatid differentiation following individualization. Ultrastructurally, dfxr mutants lose specifically the central pair microtubules in the sperm tail axoneme. The frequency of central pair microtubule loss becomes progressively greater as spermatogenesis progresses, suggesting that dFXR regulates microtubule stability. Proteomic analyses reveal that chaperones Hsp60B-, Hsp68-, Hsp90-related protein TRAP1, and other proteins have altered expression in dfxr mutant testes. Taken together with our previous nervous system results, these data suggest a common model in which dFXR regulates microtubule stability in both synaptogenesis in the nervous system and spermatogenesis in the testes. The characterization of dfxr function in the testes paves the way to genetic screens for modifiers of dfxr-induced male sterility, as a means to efficiently dissect FMRP-mediated mechanisms.
Volume 270(2)
Pages 290-307
Published 2004-6-15
DOI 10.1016/j.ydbio.2004.02.010
PII S0012160604001265
PMID 15183715
MeSH Animals Blotting, Western Disease Models, Animal Drosophila / genetics* Drosophila / physiology Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila Proteins / physiology Electrophoresis, Gel, Two-Dimensional Electrophoresis, Polyacrylamide Gel Fragile X Mental Retardation Protein Fragile X Syndrome / genetics* Immunohistochemistry Male Microscopy, Confocal Microscopy, Electron Microtubules / diagnostic imaging Microtubules / physiology* Molecular Chaperones / metabolism RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism RNA-Binding Proteins / physiology Sperm Tail / diagnostic imaging Spermatogenesis / genetics Spermatogenesis / physiology* Testis / metabolism Testis / physiology* Testis / ultrastructure Ultrasonography
IF 2.896
Times Cited 54
Drosophila DGRC#109026