TY - JOUR TI - Runx2 regulates mouse tooth root development via activation of WNT inhibitor Notum AU - Wen, Quan AU - Jing, Junjun AU - Han, Xia AU - Feng, Jifan AU - Yuan, Yuan AU - Ma, Yuanyuan AU - Chen, Shuo AU - Ho, Thach-Vu AU - Chai, Yang T2 - Journal of Bone and Mineral Research AB - Progenitor cells are crucial in controlling organ morphogenesis. Tooth development is a well-established model for investigating the molecular and cellular mechanisms that regulate organogenesis. Despite advances in our understanding of how tooth crown formation is regulated, we have limited understanding of tooth root development. RUNX2 is a well-known transcription factor in osteogenic differentiation and early tooth development. However, the function of RUNX2 during tooth root formation remains unknown. We revealed in this study that RUNX2 is expressed in a subpopulation of GLI1+ root progenitor cells, and that loss of Runx2 in these GLI1+ progenitor cells and their progeny results in root developmental defects. Our results provide in vivo evidence that Runx2 plays a crucial role in tooth root development and in regulating the differentiation of root progenitor cells. Furthermore, we identified that Gli1, Pcp4, Notum, and Sfrp2 are downstream targets of Runx2 by integrating bulk and single-cell RNA sequencing analyses. Specifically, ablation of Runx2 results in downregulation of WNT inhibitor Notum and upregulation of canonical WNT signaling in the odontoblastic site, which disturbs normal odontoblastic differentiation. Significantly, exogenous NOTUM partially rescues the impaired root development in Runx2 mutant molars. Collectively, our studies elucidate how Runx2 achieves functional specificity in regulating the development of diverse organs and yields new insights into the network that regulates tooth root development. This article is protected by copyright. All rights reserved. DO - 10.1002/jbmr.4120 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1523-4681 UR - https://asbmr.onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.4120 Y2 - 2020/06/23/17:46:19 KW - Gli1 KW - Notum KW - Runx2 KW - WNT/β-catenin KW - root development ER -