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J.-H. Joo, Y. Kim, K. Dhaduvai, S. P. Sugrue; Pnn Plays an Essential Role in Cornea Development by Influencing Neural Crest Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2586.
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© ARVO (1962-2015); The Authors (2016-present)
Depletion of Pinin (Pnn), a nuclear speckle-associated protein, in developing mouse embryos resulted in anterior segment dysgenesis, similar to Peter’s anomaly. Recently, we elucidated Pnn’s involvement in neural crest development and in the modulation of Wnt pathway. Wnt signaling pathway plays a crucial role in neural crest development. Here, we investigated how conditional inactivation of Pnn in neural crest cells affects cornea development.
Pnn was inactivated in neural crest, by mating mice harboring floxed Pnn alleles with mice expressing Cre-recombinase under the control of the Wnt1 promoter.
The deletion of Pnn in neural crest resulted in obvious cornea abnormalities with markedly reduced neural crest derived cells. Interestingly, mutant neural crest cells exhibited significantly reduced expression of platelet-derived growth factor receptor (pdgfr). In addition, Pnn depletion in mouse embryonic stem cells also led to downregulation of pdgfr. Pnn-deficiency resulted in epigenetic changes on Tcf binding elements (TBEs) of pdgfr promoter. C-terminal binding protein 2 (CtBP2), a well-known interaction partner of Pnn, was found to be a part of transcriptional regulation machinery of pdgfr promoter. Co-immunoprecipitation assays revealed a decreased association of β-catenin with CtBP2 in Pnn depleted cells.
The results suggest that Pnn is essential for cornea development through its influence on the neural crest cells and that Pnn may regulate the activity of key mediators of Wnt signaling pathway perhaps through influencing CtBP2 association with β-catenin complex.
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