AUTHOR=Jin Yong-Ri , Han Xiang Hua , Nishimori Katsuhiko , Ben-Avraham Dan , Oh Youn Jeong , Shim Jae-won , Yoon Jeong Kyo 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00264

DOI=10.3389/fcell.2020.00264

ISSN=2296-634X

ABSTRACT=<p>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 <italic>in vitro</italic> studies have clearly demonstrated the potentiation of canonical WNT signaling by RSPOs, whether this potentiation actually occurs in normal development and tissue function <italic>in vivo</italic> 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 <italic>Wnt9b</italic> and <italic>Rspo2</italic> gene knockout mice and utilizing <italic>ex vivo</italic> facial explants. <italic>Wnt9b;Rspo2</italic> double mutant mice display facial defects and dysregulated gene expression pattern that are significantly more severe than and different from those of <italic>Wnt9b</italic> or <italic>Rspo2</italic> 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.</p>