The Drosophila fragile X-related gene regulates axoneme differentiation during spermatogenesis

Dev Biol. 2004 Jun 15;270(2):290-307. doi: 10.1016/j.ydbio.2004.02.010.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • Drosophila Proteins
  • FMR1 protein, Drosophila
  • Molecular Chaperones
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein