title: Transferrin receptor facilitates TGF-β and BMP signaling activation to control craniofacial morphogenesis.
abstract: The Pierre Robin Sequence (PRS), consisting of cleft palate, glossoptosis and micrognathia, is a common human birth defect. 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's cartilage. Interestingly, Tfrc deletion dramatically suppressed both transforming growth factor-β (TGF-β) 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.
authors.affiliation: West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.|SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
authors.forename: R
authors.initials: R
authors.lastname: Lei
authors.affiliation: West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.|Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: X
authors.initials: X
authors.lastname: Shao
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Nutrition, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: F
authors.identifier: 0000-0001-8730-0003
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hong
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: West China Developmental and Stem Cell Institute, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.|SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.|Nerdbio Inc., SIP Biobay, Jiangsu 215213, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D020219:Chondrogenesis; D002972:Cleft Palate / Q000378:metabolism / Q000473:pathology; D019465:Craniofacial Abnormalities / Q000378:metabolism* / Q000473:pathology*; D017353:Gene Deletion; D008334:Mandible / Q000002:abnormalities / Q000473:pathology; D051379:Mice; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D011990:Receptors, Transferrin / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D011990:Receptors, Transferrin; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins