TY - JOUR
T1 - IFT80 is required for stem cell proliferation, differentiation, and odontoblast polarization during tooth development
AU - Yuan, Xue
AU - Cao, Xu
AU - Yang, Shuying
N1 - Funding Information:
We thank Dr. Aimee B. Stablewski and Gene Targeting and Transgenic Shared Resource at Roswell Park Cancer Institute (supported by the National Cancer Institute (NCI) grant P30CA016056) for technical assistance with the ES cell injections for generating IFT80-floxed mice. We also thank Dr. Songtao Shi for the critical reading and suggestion in the manuscript.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes during tissue development and homeostasis. However, their role in regulation of stem cell properties during tooth development remains elusive. Here, we revealed that dental pulp stem cells (DPSCs) express IFT80, which is required for maintaining DPSC properties. Mice with deletion of IFT80 in odontoblast lineage show impaired molar root development and delayed incisor eruption through reduced DPSC proliferation and differentiation, and disrupted odontoblast polarization. Impaired odontoblast differentiation resulted from disrupted hedgehog (Hh) signaling pathways. Decreased DPSC proliferation is associated with impaired fibroblast growth factor 2 (FGF2) signaling caused by loss of IFT80, leading to the disruption of FGF2-FGFR1-PI3K-AKT signaling in IFT80-deficient DPSCs. The results provide the first evidence that IFT80 controls tooth development through influencing cell proliferation, differentiation, and polarization, and Hh and FGF/AKT signaling pathways, demonstrating that IFT proteins are likely to be the new therapeutic targets for tooth and other tissue repair and regeneration.
AB - Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes during tissue development and homeostasis. However, their role in regulation of stem cell properties during tooth development remains elusive. Here, we revealed that dental pulp stem cells (DPSCs) express IFT80, which is required for maintaining DPSC properties. Mice with deletion of IFT80 in odontoblast lineage show impaired molar root development and delayed incisor eruption through reduced DPSC proliferation and differentiation, and disrupted odontoblast polarization. Impaired odontoblast differentiation resulted from disrupted hedgehog (Hh) signaling pathways. Decreased DPSC proliferation is associated with impaired fibroblast growth factor 2 (FGF2) signaling caused by loss of IFT80, leading to the disruption of FGF2-FGFR1-PI3K-AKT signaling in IFT80-deficient DPSCs. The results provide the first evidence that IFT80 controls tooth development through influencing cell proliferation, differentiation, and polarization, and Hh and FGF/AKT signaling pathways, demonstrating that IFT proteins are likely to be the new therapeutic targets for tooth and other tissue repair and regeneration.
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U2 - 10.1038/s41419-018-0951-9
DO - 10.1038/s41419-018-0951-9
M3 - Article
C2 - 30683845
AN - SCOPUS:85060529442
SN - 2041-4889
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 2
M1 - 63
ER -