title: Fibroblast growth factor signaling is essential for self-renewal of dental epithelial stem cells.
abstract: A constant supply of epithelial cells from dental epithelial stem cell (DESC) niches in the cervical loop (CL) enables mouse incisors to grow continuously throughout life. Elucidation of the cellular and molecular mechanisms underlying this unlimited growth potential is of broad interest for tooth regenerative therapies. Fibroblast growth factor (FGF) signaling is essential for the development of mouse incisors and for maintenance of the CL during prenatal development. However, how FGF signaling in DESCs controls the self-renewal and differentiation of the cells is not well understood. Herein, we report that FGF signaling is essential for self-renewal and the prevention of cell differentiation of DESCs in the CL as well as in DESC spheres. Inhibiting the FGF signaling pathway decreased proliferation and increased apoptosis of the cells in DESC spheres. Suppressing FGFR or its downstream signal transduction pathways diminished Lgr5-expressing cells in the CL and promoted cell differentiation both in DESC spheres and the CL. Furthermore, disruption of the FGF pathway abrogated Wnt signaling to promote Lgr5 expression in DESCs both in vitro and in vivo. This study sheds new light on understanding the mechanism by which the homeostasis, expansion, and differentiation of DESCs are regulated.
authors: From the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas 77030-3303.
authors: Julia Yu Fong
authors: JY
authors: Chang
authors: Cong
authors: C
authors: Wang
authors: Junchen
authors: J
authors: Liu
authors: Yanqing
authors: Y
authors: Huang
authors: Chengliu
authors: C
authors: Jin
authors: Chaofeng
authors: C
authors: Yang
authors: Bo
authors: B
authors: Hai
authors: Fei
authors: F
authors: Liu
authors: Rena N
authors: RN
authors: D'Souza
authors: Wallace L
authors: WL
authors: McKeehan
authors: Fen
authors: F
authors: Wang
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology; D014070:Tooth / Q000166:cytology*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: C493597:Lgr5 protein, mouse; D017468:Receptors, Fibroblast Growth Factor; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Development; Fibroblast Growth Factor (FGF); Fibroblast Growth Factor Receptor (FGFR); Stem Cells; Tooth; Wnt Signaling
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