Canonical Wnt/β-Catenin Signaling Regulates Postnatal Mouse Epididymal Development But Does Not Affect Epithelial Cell Differentiation

The epithelial lining of the epididymis establishes an optimal environment in which spermatozoa acquire the ability to fertilize an oocyte. This highly specialized organ develops from a simple embryonic tube known as the Wolffian duct (WD). How the simple columnar epithelium of WD acquires the complex features of the adult epididymal epithelium is currently unclear. During these first few weeks after birth, the epididymal epithelium undergoes major changes and by 5 weeks consists of four different cell types. The main objective of this study was to evaluate potential roles of Wnt signaling during postnatal epididymal development and differentiation. To analyze the activity of Wnt signaling during postnatal development, we evaluated the epididymis of TCFGFP mice, a Wnt reporter mouse model. Wnt signaling activity as indicated by green fluorescent protein expression was detected in the whole epididymis of TCFGFP mice during the first 2 weeks of life but was localized only to the caput region by 5 weeks of age. Using a genetic cell lineage tracing approach, we showed that all four of the epididymal epithelial cell types originated from the simple columnar epithelium of WD. To delineate the functional significance of epithelial Wnt signaling in epididymal development and differentiation, we generated a mouse model in which beta-catenin (Ctnnb1) was specifically ablated from the epididymal epithelium upon administration of doxycycline. Genetic suppression of epithelial Wnt/beta-catenin signaling inhibited epididymal development by affecting cell proliferation but had no effect on epithelial cell differentiation.The Wolffian duct epithelium gives rise to different epithelial cell types of the postnatal epididymis. Wnt signaling regulates the proliferation but not the differentiation of epididymal epithelium.