title: FGF8 signaling sustains progenitor status and multipotency of cranial neural crest-derived mesenchymal cells in vivo and in vitro.
abstract: The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive signals. However, what sustains the multipotency of CNC cells and derivatives remains largely unknown. In this study, we present evidence that FGF8 signaling is able to sustain progenitor status and multipotency of CNC-derived mesenchymal cells both in vivo and in vitro. We show that augmented FGF8 signaling in pre-migratory CNC cells prevents cell differentiation and organogenesis in the craniofacial region by maintaining their progenitor status. CNC-derived mesenchymal cells with Fgf8 overexpression or control cells in the presence of exogenous FGF8 exhibit prolonged survival, proliferation, and multi-potent differentiation capability in cell cultures. Remarkably, exogenous FGF8 also sustains the capability of CNC-derived mesenchymal cells to participate in organogenesis such as odontogenesis. Furthermore, FGF8-mediated signaling strongly promotes adipogenesis but inhibits osteogenesis of CNC-derived mesenchymal cells in vitro. Our results reveal a specific role for FGF8 in the maintenance of progenitor status and in fate determination of CNC cells, implicating a potential application in expansion and fate manipulation of CNC-derived cells in stem cell-based craniofacial regeneration.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA College of Life Sciences, Sichuan University, Chengdu 610041, China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Shao
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA Southern Center for Biomedical Research, Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
authors.forename: Wenduo
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA Hubei-MOST KLOS and KLOBM School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Gu
authors.affiliation: Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Congxin
authors.initials: C
authors.lastname: Lin
authors.affiliation: Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Southern Center for Biomedical Research, Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China.
authors.forename: Yanding
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China ychen@tulane.edu hutao@scu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA Southern Center for Biomedical Research, Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China ychen@tulane.edu hutao@scu.edu.cn.
authors.forename: YiPing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009432:Neural Crest / Q000166:cytology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8
keywords: FGF8; cell fate; cranial neural crest; differentiation; tooth