The Wilms’ tumor suppressor Wt1 regulates Coronin 1B expression in the epicardium

• The presence of the Eco RV (−1038)-Bam HI (−681) region is required for reporter activity of Coro1b gene.
• Wt1 is a transcriptional activator of Coro1b gene.
• Wt1 directly binds to Coro1b promoter and regulates its expression.
• The expression level of Coronin 1B is decreased in the epicardium of Wt1-deficient embryos.

Coronin 1B has been shown to be critical for cell motility and various actin-dependent processes. To understand its role more extensively, the expression and transcriptional regulation of Coro1b gene during mouse development were explored. Coronin 1B is ubiquitously expressed in the whole embryo but nevertheless shows distinct expression pattern in developing heart. In addition to the localization in endocardium, Coronin 1B is specifically expressed in the endocardial cushion and epicardium where cardiac EMT processes take place as the heart develops. Promoter deletion analysis identified the positions between −1038 and −681 is important for Coro1b basal promoter activity. In addition to a correlation of Coronin 1B localization with Wt1 expression in the epicardium, we also identified putative Wt1 binding sequences within Coro1b promoter. Direct binding of Wt1 to GC-rich sequences within the Coro1b promoter is required for the regulation of Coro1b gene expression. In accordance with the motility defect found in Coronin 1B-knockdown cells, a modest decrease in expression of Coronin 1B in the remaining epicardium of Wt1EGFPCre/EGFPCre mutant embryos was observed. These findings seem to shed light on the role of Wt1 during cell migration and suggest that, at least in part, this involves transcriptional control of Coro1b gene expression.