1. ADAR1 mediated regulation of neural crest derived melanocytes and Schwann cell development
- Author
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Gacem, Nadjet, Kavo, Anthula, Zerad, Lisa, Richard, Laurence, Mathis, Stephane, Kapur, Raj, Parisot, Mélanie, Amiel, Jeanne, de La Grange, Pierre, Pingault, Veronique, Vallat, Jean, Bondurand, Nadege, Dufour, Sylvie, Embryology and genetics of human malformation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Morphogénèse et Génétique Moléculaire [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Neurology [Limoges], Centre de référence national neuropathies périphériques rares [CHU Limoges], CHU Limoges-CHU Limoges, Nerve-Muscle Unit [Bordeaux], Department of Neurology [Bordeaux], Grand Sud-Ouest National Reference Center for Neuromuscular Disorders [Bordeaux], Pellegrin Hospital [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]-Pellegrin Hospital [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]-Grand Sud-Ouest National Reference Center for Neuromuscular Disorders [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], University of Washington [Seattle], Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GenoSplice [Paris], Service de Génétique Moléculaire [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Eq. 6 - Morphogenèse et génétique moléculaire (Inserm U955 - IMRB), This work was supported by the Fondation ARC pour la recherche sur le cancer and AFM trampoline grant to N.B., Institut National Pour la Santé de la Recherche Médicale (INSERM), state funding from the Agence Nationale de la Recherche under the 'Investissements d’avenir' program [ANR-10-IAHU-01] and the MSDAvenir fund [DEVO—DECODE project]. N.G. and A.K. both received a 3-year Ph.D. fellowship from ED-SVS402, L.Z. received a 3-year Ph.D. fellowship from ED-BioSPC. N.G. is a beneficiary of an Institut Imagine 4th-year Ph.D. fellowship (7 months) from Fondation Bettencourt Schueller and supported by Fondation des treilles., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Bodescot, Myriam, and Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID
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RNA editing ,Adenosine Deaminase ,Science ,Neurogenesis ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Article ,Mice ,Developmental biology ,Animals ,lcsh:Science ,Skin ,Mice, Knockout ,[SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Heart ,Sciatic Nerve ,Up-Regulation ,Disease Models, Animal ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Neural Crest ,embryonic structures ,Melanocytes ,lcsh:Q ,Interferons ,Schwann Cells ,Transcriptome ,Gene Deletion - Abstract
The neural crest gives rise to numerous cell types, dysfunction of which contributes to many disorders. Here, we report that adenosine deaminase acting on RNA (ADAR1), responsible for adenosine-to-inosine editing of RNA, is required for regulating the development of two neural crest derivatives: melanocytes and Schwann cells. Neural crest specific conditional deletion of Adar1 in mice leads to global depigmentation and absence of myelin from peripheral nerves, resulting from alterations in melanocyte survival and differentiation of Schwann cells, respectively. Upregulation of interferon stimulated genes precedes these defects, which are associated with the triggering of a signature resembling response to injury in peripheral nerves. Simultaneous extinction of MDA5, a key sensor of unedited RNA, rescues both melanocytes and myelin defects in vitro, suggesting that ADAR1 safeguards neural crest derivatives from aberrant MDA5-mediated interferon production. We thus extend the landscape of ADAR1 function to the fields of neural crest development and disease., ADAR1 is an RNA editing protein known to regulate immune responses to dsRNA that has been connected to neural crest cell function. Here, the authors show RNA editing by ADAR1 is important for the normal development of neural crest derived melanocytes and Schwann cells.
- Published
- 2020