The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective.
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TLDR
The role of NDD-associated chromatin remodelers during the developmental continuum of progenitor expansion, differentiation, cell-type specification, migration and maturation is detailed.Abstract:
Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum disorders (ASD), are a large group of disorders in which early insults during brain development result in a wide and heterogeneous spectrum of clinical diagnoses. Mutations in genes coding for chromatin remodelers are overrepresented in NDD cohorts, pointing towards epigenetics as a convergent pathogenic pathway between these disorders. In this review we detail the role of NDD-associated chromatin remodelers during the developmental continuum of progenitor expansion, differentiation, cell-type specification, migration and maturation. We discuss how defects in chromatin remodelling during these early developmental time points compound over time and result in impaired brain circuit establishment. In particular, we focus on their role in the three largest cell populations: glutamatergic neurons, GABAergic neurons, and glia cells. An in-depth understanding of the spatiotemporal role of chromatin remodelers during neurodevelopment can contribute to the identification of molecular targets for treatment strategies.read more
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TL;DR: Perturbation of ChD8 in adult mice recapitulates improved acquired motor learning behavior found in Chd8+/- animals, suggesting a role for CHD 8 in adult striatal circuits, and support a mechanism linking chromatin modification to striatal dysfunction and the molecular pathology of ASD.
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Missense variants in DPYSL5 cause a neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Médéric Jeanne,Hélène Demory,Aubin Moutal,Marie Laure Vuillaume,Sophie Blesson,Rose Anne Thépault,Sylviane Marouillat,Judith Halewa,Saskia M. Maas,M. Mahdi Motazacker,Grazia M.S. Mancini,Marjon van Slegtenhorst,Avgi Andreou,Helene Cox,Julie Vogt,Jason Laufman,Natella Kostandyan,Davit Babikyan,Miroslava Hancarova,Sarka Bendova,Zdenek Sedlacek,Kimberly A. Aldinger,Elliott H. Sherr,Emanuela Argilli,Eleina M. England,Séverine Audebert-Bellanger,Dominique Bonneau,Estelle Colin,Anne Sophie Denommé-Pichon,Brigitte Gilbert-Dussardier,Bertrand Isidor,Sébastien Küry,Sylvie Odent,Richard Redon,Rajesh Khanna,William B. Dobyns,William B. Dobyns,Stéphane Bézieau,Jérôme Honnorat,Bernhard Lohkamp,Annick Toutain,Frédéric Laumonnier +41 more
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