Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation

Xiaolin Tu, Kyu Sang Joeng, Keiichi I. Nakayama, Keiko Nakayama, Jayaraj Rajagopal, Thomas J Carroll, Andrew P. McMahon, Fanxin Long

Research output: Contribution to journalArticle

216 Scopus citations


Wnt signaling regulates a variety of developmental processes in animals. Although the β-catenin-dependent (canonical) pathway is known to control cell fate, a similar role for noncanonical Wnt signaling has not been established in mammals. Moreover, the intracellular cascades for noncanonical Wnt signaling remain to be elucidated. Here, we delineate a pathway in which Wnt3a signals through the Gαq/11 subunits of G proteins to activate phosphatidylinositol signaling and PKCδ in the murine ST2 cells. Gαq/11-PKCδ signaling is required for Wnt3a-induced osteoblastogenesis in these cells, and PKCδ homozygous mutant mice exhibit a deficit in embryonic bone formation. Furthermore, Wnt7b, expressed by osteogenic cells in vivo, induces osteoblast differentiation in vitro via the PKCδ-mediated pathway; ablation of Wnt7b in skeletal progenitors results in less bone in the mouse embryo. Together, these results reveal a Wnt-dependent osteogenic mechanism, and they provide a potential target pathway for designing therapeutics to promote bone formation.

Original languageEnglish (US)
Pages (from-to)113-127
Number of pages15
JournalDevelopmental Cell
Issue number1
StatePublished - Jan 1 2007




ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Tu, X., Joeng, K. S., Nakayama, K. I., Nakayama, K., Rajagopal, J., Carroll, TJ., McMahon, A. P., & Long, F. (2007). Noncanonical Wnt Signaling through G Protein-Linked PKCδ Activation Promotes Bone Formation. Developmental Cell, 12(1), 113-127.