Canonical WNT/β-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice
- Front Cell Dev Biol. 2020 May 8:8:264. doi: 10.3389/fcell.2020.00264.
- 1. Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, United States.
- 2. Department of Applied Biological Chemistry, Tohoku University, Sendai, Japan.
- 3. Nancy and Stephen Grand Israel National Center for Personalized Medicine, Mantoux Institute for Bioinformatics, Weizmann Institute of Science, Rehovot, Israel.
- 4. Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan-si, South Korea.
- 5. Department of Integrated Biomedical Science, Soonchunhyang University, Cheonan-si, South Korea.
The R-spondin (RSPO) family of proteins potentiate canonical Wnt/β-catenin signaling and may provide a mechanism to fine-tune the strength of canonical Wnt signaling. Although several in vitro studies have clearly demonstrated the potentiation of canonical Wnt signaling by RSPOs, whether this potentiation actually occurs in normal development and tissue function in vivo still remains poorly understood. Here, we provide clear evidence of the potentiation of canonical Wnt signaling by RSPO during mouse facial development by analyzing compound Wnt9b and Rspo2 gene knockout mice and utilizing ex vivo facial explants. Wnt9b;Rspo2 double mutant mice display facial defects and dysregulated gene expression pattern that are significantly more severe than and different from those of Wnt9b or Rspo2 null mutant mice. Furthermore, we found suggestive evidence that the LGR4/5/6 family of the RSPO receptors may play less critical roles in WNT9b:RSPO2 cooperation. Our results suggest that RSPO-induced cooperation is a key mechanism for fine-tuning canonical Wnt/β-catenin signaling in mouse facial development.