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However, how this abnormality occurs remains largely unknown. Here we report that neural crest cell (NCC)-specific knockout of transferrin receptor (Tfrc), a well known transferrin transporter protein, caused micrognathia, cleft palate, severe respiratory distress and inability to suckle in mice, which highly resemble human PRS. Histological and anatomical analysis revealed that the cleft palate is due to the failure of palatal shelves elevation that resulted from a retarded extension of Meckel\u2019s cartilage. Interestingly, <jats:italic>Tfrc<\/jats:italic> deletion dramatically suppressed both transforming growth factor-<jats:italic>\u03b2<\/jats:italic> (TGF-<jats:italic>\u03b2<\/jats:italic>) and bone morphogenetic protein (BMP) signaling in cranial NCCs-derived mandibular tissues, suggesting that Tfrc may act as a facilitator of these two signaling pathways during craniofacial morphogenesis. Together, our study uncovers an unknown function of Tfrc in craniofacial development and provides novel insight into the etiology of PRS.<\/jats:p>","DOI":"10.1038\/cddis.2016.170","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T13:05:05Z","timestamp":1467291905000},"page":"e2282-e2282","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Transferrin receptor facilitates TGF-\u03b2 and BMP signaling activation to control craniofacial morphogenesis"],"prefix":"10.1038","volume":"7","author":[{"given":"R","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-0003","authenticated-orcid":false,"given":"F","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,30]]},"reference":[{"key":"BFcddis2016170_CR1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/bdrc.20013","volume":"72","author":"PG Farlie","year":"2004","unstructured":"Farlie PG, McKeown SJ, Newgreen DF . 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