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

Nadjet Gacem 1, 2 Anthula Kavo 2, 3 Lisa Zerad 1 Laurence Richard 4 Stephane Mathis 5 Raj Kapur 6 Mélanie Parisot 7 Jeanne Amiel 1 Sylvie Dufour 2, 3 Pierre de la Grange 8 Veronique Pingault 1, 9 Jean Vallat 4 Nadege Bondurand 1, 2, *
* Corresponding author
1 Equipe Inserm U1163 - Embryology and genetics of human malformation
IMAGINE - U1163 - Imagine - Institut des maladies génétiques
2 Morphogénèse et Génétique Moléculaire [Créteil]
IMRB - Institut Mondor de Recherche Biomédicale
4 Department of Neurology [Limoges]
Centre de référence national neuropathies périphériques rares [CHU Limoges]
5 Nerve-Muscle Unit [Bordeaux]
Department of Neurology [Bordeaux]
7 Plateforme de génomique [SFR Necker]
SFR Necker - UMS 3633 / US24 - Structure Fédérative de Recherche Necker
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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Submitted on : Friday, February 28, 2020 - 2:50:00 PM
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Nadjet Gacem, Anthula Kavo, Lisa Zerad, Laurence Richard, Stephane Mathis, et al.. ADAR1 mediated regulation of neural crest derived melanocytes and Schwann cell development. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.198. ⟨10.1038/s41467-019-14090-5⟩. ⟨inserm-02494188⟩

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