title: Essential role of citron kinase in cytokinesis of spermatogenic precursors.
abstract: During spermatogenesis, the first morphological indication of spermatogonia differentiation is incomplete cytokinesis, followed by the assembly of stable intercellular cytoplasmic communications. This distinctive feature of differentiating male germ cells has been highly conserved during evolution, suggesting that regulation of the cytokinesis endgame is a crucial aspect of spermatogenesis. However, the molecular mechanisms underlying testis-specific regulation of cytokinesis are still largely unknown. Citron kinase is a myotonin-related protein acting downstream of the GTPase Rho in cytokinesis control. We previously reported that Citron kinase knockout mice are affected by a complex neurological syndrome caused by cytokinesis block and apoptosis of specific neuronal precursors. In this report we show that, in addition, these mice display a dramatic testicular impairment, with embryonic and postnatal loss of undifferentiated germ cells and complete absence of mature spermatocytes. By contrast, the ovaries of mutant females appear essentially normal. Developmental analysis revealed that the cellular depletion observed in mutant testes is caused by increased apoptosis of undifferentiated and differentiating precursors. The same cells display a severe cytokinesis defect, resulting in the production of multinucleated cells and apoptosis. Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line.
authors.affiliation: Department of Genetics, Biology and Biochemistry, Via Santena 5 bis, Torino, Italy. ferdinando.dicunto@unito.it
authors.forename: Ferdinando Di
authors.initials: FD
authors.lastname: Cunto
authors.forename: Sara
authors.initials: S
authors.lastname: Imarisio
authors.forename: Paola
authors.initials: P
authors.lastname: Camera
authors.forename: Carla
authors.initials: C
authors.lastname: Boitani
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D013090:Spermatocytes / Q000166:cytology*; D013737:Testis / Q000166:cytology / Q000201:enzymology / Q000254:growth & development
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases