Fig. 3

In the absence of β-catenin, TCF/LEF-1 and Groucho can form a complex and suppress transcriptional events. When Wnt signaling is activated, and β-catenin is stabilized, Groucho is displaced, and it binds TCF/LEF-1 causing a transcriptional activation. In our case, XXYLT1 deletion leads to impaired Notch xylosylation, causing abnormally up-regulated Notch function. This process decreases β-catenin and increases HES-1, which interacts with Groucho and prevents the following activation of gene transcriptions. As a result, osteoblastogenesis mediated by Wnt/β-catenin is inhibited by over-functional Notch signaling, which may contribute to the pathogenic process and finally lead to the congenital skeletal defects observed in our patient