Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4

Bergeron, Karl-F.; Nguyen, Chloé M. A.; Cardinal, Tatiana; Charrier, Baptiste; Silversides, David W. et Pilon, Nicolas (2016). « Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4 ». Disease Models & Mechanisms, 9(11), pp. 1283-1293.

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Résumé

Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line – obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC) development – is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4.

Type:	Article de revue scientifique
Informations complémentaires:	Cet article a été publié à: http://dmm.biologists.org/content/9/11/1283
Mots-clés ou Sujets:	Enteric nervous system, Hirschsprung disease, Melanocytes, Mouse model, Neural crest cells, Waardenburg syndrome
Unité d'appartenance:	Centres institutionnels > Centre de recherches biomédicales (BIOMED) Faculté des sciences > Département des sciences biologiques
Déposé par:	Jean-Jacques Rondeau
Date de dépôt:	07 déc. 2018 09:11
Dernière modification:	07 déc. 2018 09:11
Adresse URL :	http://archipel.uqam.ca/id/eprint/11967

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