Meyer R.E.,French National Center for Scientific Research |
Meyer R.E.,Oklahoma Medical Research Foundation |
Delaage M.,IBDML |
Rosset R.,IBDML |
And 3 more authors.
Background: Sexual reproduction relies on two key events: formation of cells with a haploid genome (the gametes) and restoration of diploidy after fertilization. Therefore the underlying mechanisms must have been evolutionary linked and there is a need for evidence that could support such a model.Results: We describe the identification and the characterization of yem1, the first yem-alpha mutant allele (V478E), which to some extent affects diploidy reduction and its restoration. Yem-alpha is a member of the Ubinuclein/HPC2 family of proteins that have recently been implicated in playing roles in chromatin remodeling in concert with HIRA histone chaperone. The yem1mutant females exhibited disrupted chromosome behavior in the first meiotic division and produced very low numbers of viable progeny. Unexpectedly these progeny did not display paternal chromosome markers, suggesting that they developed from diploid gametes that underwent gynogenesis, a form of parthenogenesis that requires fertilization.Conclusions: We focus here on the analysis of the meiotic defects exhibited by yem1oocytes that could account for the formation of diploid gametes. Our results suggest that yem1affects chromosome segregation presumably by affecting kinetochores function in the first meiotic division.This work paves the way to further investigations on the evolution of the mechanisms that support sexual reproduction. © 2010 Meyer et al; licensee BioMed Central Ltd. Source
Napoletano F.,San Raffaele Scientific Institute |
Occhi S.,San Raffaele Scientific Institute |
Calamita P.,San Raffaele Scientific Institute |
Volpi V.,Kings College London |
And 5 more authors.
Large alterations in transcription accompany neurodegeneration in polyglutamine (polyQ) diseases. These pathologies manifest both general polyQ toxicity and mutant protein-specific effects. In this study, we report that the fat tumour suppressor gene mediates neurodegeneration induced by the polyQ protein Atrophin. We have monitored early transcriptional alterations in a Drosophila model of Dentatorubral-pallidoluysian Atrophy and found that polyQ Atrophins downregulate fat. Fat protects from neurodegeneration and Atrophin toxicity through the Hippo kinase cascade. Fat/Hippo signalling does not provoke neurodegeneration by stimulating overgrowth; rather, it alters the autophagic flux in photoreceptor neurons, thereby affecting cell homeostasis. Our data thus provide a crucial insight into the specific mechanism of a polyQ disease and reveal an unexpected neuroprotective role of the Fat/Hippo pathway. © 2011 European Molecular Biology Organization. Source