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J Mol Cell Biol. 2015 Oct;7(5):441-54. doi: 10.1093/jmcb/mjv052. Epub 2015 Aug 4.

FGF8 signaling sustains progenitor status and multipotency of cranial neural crest-derived mesenchymal cells in vivo and in vitro.

Author information

1
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.
2
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
3
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.
4
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.
5
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Southern Center for Biomedical Research, Fujian Key Laboratory of Developmental and Neural Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China.
7
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
8
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China ychen@tulane.edu hutao@scu.edu.cn.
9
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.

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.

KEYWORDS:

FGF8; cell fate; cranial neural crest; differentiation; tooth

PMID:
26243590
PMCID:
PMC4589951
DOI:
10.1093/jmcb/mjv052
[Indexed for MEDLINE]
Free PMC Article

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