Cyclin G deregulation, a tool to decipher gene network(s) controlling developmental stability
Résumé
Developmental stability, or the buffering of developmental noise, is of paramount importance to maintain symmetry in bilaterians. Noisiness of growth can cause noisiness in organ size, which translates into imperfect symmetry. In an isogenic population bred in a standardized environment, developmental stability can be estimated by fluctuating asymmetry (FA), the random deviation from perfect symmetry. However, addressing the cellular and genetic bases of developmental stability has long been impeded by the very low amplitude of FA in control Drosophila lines. We have recently shown that overexpression of the Cyclin G gene (CycG) induces extremely high FA in different organs of the fly (up to 40-fold increase in wings). This suggests that CycG might be a hub in a gene network underlying developmental stability. Deregulation of CycG thus provides a unique tool to decipher such a network [1,2]. Cyclin G binds two chromatin regulators of the Enhancers of Polycomb and Trithorax (ETP) family via its ETP-interacting domain, and is involved in transcriptional control [3]. Moreover, Cyclin G negatively controls the cell cycle by slowing down the G1 and S phases, and directly interacts with CDK2 and CDK4 [4]. Lastly, CycG deregulation impairs the tight correlation that normally exists between cell size and cell number in fly wings [1]. Based on these features, we are addressing the molecular and genetic bases of developmental stability. First, we are analyzing wing FA and cell parameters in flies overexpressing truncated forms of CycG (deleted of either the ETP-interacting domain or the cyclin domain). Second, we are identifying Cyclin G transcriptional targets by RNA-seq. Third, we are carrying out a candidate gene approach (using mutants for Cyclin G interactors, transcriptional targets etc…) to isolate modifiers of the CycG-induced FA phenotype.These modifiers will then be assembled to build the first gene network focused on developmental stability and symmetry maintenance in a bilaterian.
Domaines
Sciences du Vivant [q-bio]
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