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• W2469851805 abstract "Event Abstract Back to Event DMRT transcription factors are required for cortical development Marc Keruzore1, Sarah De Clercq1, Elodie Desmaris1 and Eric Bellefroid1* 1 University of Brussel, Developmental Genetics, Belgium Patterning the cerebral hemispheres and generating the neocortical area map depend initially on interplay between morphogens secreted by organizing centers and transcription factors expressed in gradients across the cortical primordium. One of the latter, Dmrt5/Dmrta2, a zinc finger doublesex and mab-3 related (Dmrt) gene, is expressed in mouse cortical progenitors in a high caudomedial to low rostrolateral gradient. Dmrt5 is required for the development of caudomedial cerebral cortex but its mode of action remains unclear. In constitutively Dmrt5 null mice, the Wnt-and Bmp-rich cortical hem is missing, suggesting that hem formation relies on DMRT5, and that deletion of Dmrt5 affects cortical patterning indirectly through loss of signalling from the hem (Saulnier et al., 2013). In a positive feedback loop however, WNT signalling upregulates Dmrt5 expression, suggesting a second, direct patterning role for DMRT5. Our recent data indicate that inactivating or overexpressing Dmrt5 conditionally in cortical progenitors close to midgestation still affect cortical patterning without disrupting the function of the hem and that mutation of a related gene, Dmrt3, with a similar expression pattern to Dmrt5, also caused similar, albeit milder cortical patterning defects than that observed in Dmrt5 mutants. Thus, Dmrt5 and Dmrt3 appears to have direct roles in cortical patterning, in addition to their prior role in the establishment of the cortical hem (De Clercq et al., 2015). Analysis of the cortex of Dmrt3-/-;Dmrt5-/- double knock-out mice reveals that the phenotype is more severe than in the single mutants, suggesting that the two genes cooperates to control cortical patterning. RNA-seq and ChIP-seq analyses are underway to identify their direct targets. Résumé en Français Des anomalies de développement du cortex cérébral sont à l’origine de nombreuses maladies neuropsychiatriques et neurologiques chez l’homme. Nos travaux ont montré que chez la souris, les facteurs de transcription Dmrt3/5 jouent un rôle essentiel dans le développement cortical, en particulier dans la formation des aires du néocortex. Chez l’homme, des mutations dans le gène DMRT5 ont été identifiées associées à une microcéphalie. Le but de nos travaux est de mieux comprendre leur mécanisme d'action dans le contrôle de la prolifération et la différenciation des progéniteurs corticaux. Samenvatting in het Nederlands: Ontwikkelingsstoornissen van de hersenschors liggen aan de basis van tal van neuropsychiatrische en neurologische ziekten bij de mens. Ons werk heeft aangetoond dat bij muizen, de transcriptiefactoren Dmrt3/5 een essentiële rol spelen in de ontwikkeling van de hersenschors, meer bijzonder in de vorming van de gebieden van de neocortex. Mutaties van het genDMRT5 bij de mens werden geïdentificeerd en geassocieerd aan een microcefalie. Het doel van ons werk is een beter begrip van hun werking in de controle van de verspreiding en de differentiering van de ontwikkeling van de hersenschors. Acknowledgements Marc Keruzore and Sarah De Clercq contributed equally to the work References Saulnier A. et al. (2013). The doublesex homolog Dmrt5 is required for the development of the caudomedial cerebral cortex in mammals. Cerebral Cortex, 23, 2552-2567. De Clerq S. et al. (2016). Dmrt5 directs neocortical patterning together with Dmrt3 and is controlled by negative autoregulation. Cerebral Cortex, submitted, manuscript under revision. Keywords: cortical hem, Hippocampus, Neocortex, primary visual area, Transcription Factors Conference: 6th Belgian Brain Congress, MONS, Belgium, 8 Oct - 8 Oct, 2016. Presentation Type: Poster Presentation Topic: Brain and brain diseases: between heredity and environment Citation: Keruzore M, De Clercq S, Desmaris E and Bellefroid E (2016). DMRT transcription factors are required for cortical development. Conference Abstract: 6th Belgian Brain Congress. doi: 10.3389/conf.fnagi.2016.03.00034 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2016; Published Online: 04 Jul 2016. * Correspondence: Prof. Eric Bellefroid, University of Brussel, Developmental Genetics, Gosselies, 6041, Belgium, ebellefr@ulb.ac.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marc Keruzore Sarah De Clercq Elodie Desmaris Eric Bellefroid Google Marc Keruzore Sarah De Clercq Elodie Desmaris Eric Bellefroid Google Scholar Marc Keruzore Sarah De Clercq Elodie Desmaris Eric Bellefroid PubMed Marc Keruzore Sarah De Clercq Elodie Desmaris Eric Bellefroid Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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• W2469851805 title "DMRT5 directs neocortical area patterning together with DMRT3" @default.
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