Canonical WNT/β-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice
Autor: | Yong-Ri Jin, Xiang Hua Han, Katsuhiko Nishimori, Dan Ben-Avraham, Youn Jeong Oh, Jae-won Shim, Jeong Kyo Yoon |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Morphogenesis Biology cleft lip facial development 03 medical and health sciences Cell and Developmental Biology 0302 clinical medicine Gene expression Wnt9b WNT signaling Receptor RSPO2 lcsh:QH301-705.5 RSPO2 Gene Original Research cleft palate Wnt signaling pathway Long-term potentiation Cell Biology Cell biology 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis Knockout mouse R-spondin2 Developmental Biology |
Zdroj: | Frontiers in Cell and Developmental Biology, Vol 8 (2020) Frontiers in Cell and Developmental Biology |
Popis: | 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. |
Databáze: | OpenAIRE |
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