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Nat Commun. 2020 Jan 10;11(1):198. doi: 10.1038/s41467-019-14090-5.

ADAR1 mediated regulation of neural crest derived melanocytes and Schwann cell development.

Author information

1
Laboratory of Embryology and Genetics of Human Malformation, Imagine Institute, INSERM UMR 1163, Universite Paris Descartes-Universite de Paris, Paris, France.
2
INSERM, U955, Equipe 06, 8, rue du General Sarrail, 94010, Creteil Cedex, France.
3
Faculte de Medecine, Universite Paris Est, 94000, Creteil, France.
4
Department of Neurology, Centre de Reference Neuropathies Peripheriques Rares, 2 avenue Martin-Luther-King, 87042, Limoges, France.
5
Department of Neurology (Nerve-Muscle Unit) and Grand Sud-Ouest National Reference Center for Neuromuscular Disorders, CHU Bordeaux, Pellegrin Hospital, 33076, Bordeaux, France.
6
Department of Pathology, Seattle Children's Hospital and University of Washington, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.
7
Genomics Core Facility, Institut Imagine-Structure Federative de Recherche Necker, INSERM U1163 and INSERM US24/CNRS UMS3633, 24 bvd Montparnasse, 75015, Paris, France.
8
GenoSplice, Paris, France.
9
Service de Genetique Moleculaire, Hopital Necker-Enfants-Malades, 149 rue de Sevres, 75015, Paris, France.
10
Laboratory of Embryology and Genetics of Human Malformation, Imagine Institute, INSERM UMR 1163, Universite Paris Descartes-Universite de Paris, Paris, France. nadege.bondurand@inserm.fr.
11
INSERM, U955, Equipe 06, 8, rue du General Sarrail, 94010, Creteil Cedex, France. nadege.bondurand@inserm.fr.

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.

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