Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis.

Developmental Biology
Jeong-Hoon JooStephen P Sugrue

Abstract

Pinin (Pnn), a nuclear speckle-associated protein, has been shown to function in maintenance of epithelial integrity through altering expression of several key adhesion molecules. Here we demonstrate that Pnn plays a crucial role in small intestinal development by influencing expression of an intestinal homeobox gene, Cdx2. Conditional inactivation of Pnn within intestinal epithelia resulted in significant downregulation of a caudal type homeobox gene, Cdx2, leading to obvious villus dysmorphogenesis and severely disrupted epithelial differentiation. Additionally, in Pnn-deficient small intestine, we observed upregulated Tcf/Lef reporter activity, as well as misregulated expression/distribution of beta-catenin and Tcf4. Since regulation of Cdx gene expression has been closely linked to Wnt/beta-catenin signaling activity, we explored the possibility of Pnn's interaction with beta-catenin, a major effector of the canonical Wnt signaling pathway. Co-immunoprecipitation assays revealed that Pnn, together with its interaction partner CtBP2, a transcriptional co-repressor, was in a complex with beta-catenin. Moreover, both of these proteins were found to be recruited to the proximal promoter area of Cdx2. Taken together, our results...Continue Reading

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Citations

Mar 26, 2011·Histochemistry and Cell Biology·Shu-Yuan HsuPin Ouyang
Mar 1, 2012·Histochemistry and Cell Biology·Stefan Hübner, Athina Efthymiadis
Apr 25, 2012·Histochemistry and Cell Biology·Shu-Yuan HsuPin Ouyang
Jan 20, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jason R SpenceNoah F Shroyer
Aug 4, 2016·Scientific Reports·Sunil K VermaMuge N Kuyumcu-Martinez
Oct 14, 2017·Bioinformatics·Zeljko TomljanovicAndrew F Teich
Mar 6, 2012·Nature Structural & Molecular Biology·Andrea Giovanni MurachelliElena Conti
Apr 23, 2020·International Journal of Molecular Medicine·Antonios KostourosJohn Tsiaoussis

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