Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Takamitsu MaruyamaWei Hsu

Abstract

Recent identification and isolation of suture stem cells capable of long-term self-renewal, clonal expanding, and differentiating demonstrate their essential role in calvarial bone development, homeostasis, and injury repair. These bona fide stem cells express a high level of Axin2 and are able to mediate bone regeneration and repair in a cell autonomous fashion. The importance of Axin2 is further demonstrated by its genetic inactivation in mice causing skeletal deformities resembling craniosynostosis in humans. The fate determination and subsequent differentiation of Axin2+ stem cells are highly orchestrated by a variety of evolutionary conserved signaling pathways including Wnt, FGF, and BMP. These signals are often antagonistic of each other and possess differential effects on osteogenic and chondrogenic cell types. However, the mechanisms underlying the interplay of these signaling transductions remain largely elusive. Here we identify Rap1b acting downstream of Axin2 as a signaling interrogator for FGF and BMP. Genetic analysis reveals that Rap1b is essential for development of craniofacial and body skeletons. Axin2 regulates Rap1b through modulation of canonical BMP signaling. The BMP-mediated activation of Rap1b promotes...Continue Reading

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Citations

Aug 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Andrew T TimberlakeRichard P Lifton
Oct 19, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·H-M Ivy YuWei Hsu
Jul 10, 2019·Stem Cells International·Jun-Qi LiuZhen Tan
Jun 25, 2020·International Journal of Molecular Sciences·Lorena Di PietroWanda Lattanzi
Mar 5, 2021·Science Translational Medicine·Takamitsu MaruyamaWei Hsu
Aug 20, 2021·Biochemical Genetics·Baojin YaoDaqing Zhao
Aug 28, 2021·Biomolecules·Bo LiLongjiang Li

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