IFT80 is required for stem cell proliferation, differentiation, and odontoblast polarization during tooth development

Xue Yuan,Shuying Yang,Xu Cao

doi:10.1038/s41419-018-0951-9

Abstract

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.

Highlights

Tooth development, like many other organs’ formation, requires multi-lineage cells controlled by different signaling pathways
In addition to the morphology changes, we found that the expression of odontoblast marker genes (DMP1 and dentin sialophosphoprotein (DSPP)) in dental pulp was strikingly reduced in OSX;IFT80f/f mice by quantitative PCR (Fig. 3e), confirming that IFT80 deletion impaired odontoblast differentiation
Discussion primary cilia have been observed in dental pulp stem cells (DPSCs) and odontoblasts more than a decade ago[27], the function of primary cilia and intraflagellar transport (IFT) proteins in DPSCs has not been well addressed

Summary

Introduction

Like many other organs’ formation, requires multi-lineage cells controlled by different signaling pathways. During tooth formation, a subpopulation of mesenchymal cells differentiates into odontoblasts, which are the columnar polarized cells located at the outer edges of dental pulp, expressing dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP), and producing dentin. Dental pulp is the soft tissue inside the tooth, and their function is to support dentin formation and regeneration[1,2]. Formation and function of primary cilia require intraflagellar transport (IFT) proteins and other ciliary proteins[3,4]. Mutation of those proteins usually causes cilia defects, leading to a wide range of diseases called ciliopathies. These disorders target multiple tissues, of which bone and tooth are most common tissues[5–7]

Methods

Results

Conclusion