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Canonical WNT/?-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice.


ABSTRACT: The R-spondin (RSPO) family of proteins potentiate canonical WNT/?-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/?-catenin signaling in mouse facial development.

SUBMITTER: Jin YR 

PROVIDER: S-EPMC7225269 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Canonical WNT/β-Catenin Signaling Activated by WNT9b and RSPO2 Cooperation Regulates Facial Morphogenesis in Mice.

Jin Yong-Ri YR   Han Xiang Hua XH   Nishimori Katsuhiko K   Ben-Avraham Dan D   Oh Youn Jeong YJ   Shim Jae-Won JW   Yoon Jeong Kyo JK  

Frontiers in cell and developmental biology 20200508


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 <i>in vitro</i> studies have clearly demonstrated the potentiation of canonical WNT signaling by RSPOs, whether this potentiation actually occurs in normal development and tissue function <i>in vivo</i> still remains poorly understood. Here, we provide clear evidence of the potentiation of canonical WNT signaling b  ...[more]

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