{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:14:59Z","timestamp":1791339299983,"version":"4.3.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T00:00:00Z","timestamp":1657929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Waardenburg syndrome type 4 (WS4) combines abnormal development of neural crest cell (NCC)\u2010derived melanocytes (causing depigmentation and inner ear dysfunction) and enteric nervous system (causing aganglionic megacolon). The full spectrum of WS4 phenotype is present in <jats:italic>Spot<\/jats:italic> mice, in which an insertional mutation close to a silencer element leads to NCC\u2010specific upregulation of the transcription factor\u2010coding gene <jats:italic>Nr2f1<\/jats:italic>. These mice were previously found to develop aganglionic megacolon because of NR2F1\u2010induced premature differentiation of enteric neural progenitors into enteric glia. Intriguingly, this prior work also showed that inner ear dysfunction in <jats:italic>Spot<\/jats:italic> mutants specifically affects balance but not hearing, consistent with the absence of melanocytes in the vestibule only. Here, we report an analysis of the effect of <jats:italic>Nr2f1<\/jats:italic> upregulation on the development of both inner ear and skin melanocytes, also taking in consideration their origin relative to the dorsolateral and ventral NCC migration pathways. In the trunk, we found that NR2F1 overabundance in <jats:italic>Spot<\/jats:italic> NCCs forces dorso\u2010laterally migrating melanoblasts to abnormally adopt a Schwann cell precursor (SCP) fate and conversely prevents ventrally migrating SCPs to normally adopt a melanoblast fate. In the head, <jats:italic>Nr2f1<\/jats:italic> upregulation appears not to be uniform, which might explain why SCP\u2010derived melanocytes do colonize the cochlea while non\u2010SCP\u2010derived melanocytes cannot reach the vestibule. Collectively, these data point to a key role for NR2F1 in the control of SCP\u2010vs\u2010melanocyte fate choice and unveil a new pathogenic mechanism for WS4. Moreover, our data argue against the proposed existence of a transit\u2010amplifying compartment of melanocyte precursors in hair follicles.<\/jats:p>","DOI":"10.1111\/pcmr.13054","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T15:59:43Z","timestamp":1657555183000},"page":"506-516","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>NR2F1<\/scp> regulates a Schwann cell precursor\u2010vs\u2010melanocyte cell\u00a0fate switch in a mouse model of Waardenburg syndrome type <scp>IV<\/scp>"],"prefix":"10.1111","volume":"35","author":[{"given":"Gr\u00e9goire","family":"Bonnamour","sequence":"first","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Canada"},{"name":"Centre d'Excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Charrier","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Canada"},{"name":"Centre d'Excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sephora","family":"Sallis","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Canada"},{"name":"Centre d'Excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Leduc","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Canada"},{"name":"Centre d'Excellence en Recherche sur les Maladies Orphelines\u2014Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3641-0776","authenticated-orcid":false,"given":"Nicolas","family":"Pilon","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory, D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Canada"},{"name":"Centre 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