Organ shape and size is an important determinant of their physiological functions. How tubal organs get their shape is a fundamental question in biology. Mouse epididymis (Wolffian duct) goes through remarkable changes during development, where almost a meter long duct fits into a small space by the extensive coiling of epithelial cells. The Wolffian duct develops as a simple straight tube, which after 15.5 day post coitum, undergoes coiling to form a highly convoluted tube. Genetic ablation studies in mouse models have shown that androgen receptor signalling is not essential for epididymal coiling, suggesting that other autocrine and/or paracrine signals play an important role in determining epididymal shape.
Canonical Wnt signalling is involved in the development of various organs and its deregulation leads to developmental defects and cancer. To understand the physiological significance of the Wnt pathway in male reproductive tract organogenesis, we studied real time changes in Wnt activity during different stages of development using a Wnt reporter mouse model. We detected active Wnt signals across the epithelium of the Wolffian duct. However, in adult mice, Wnt signalling was limited to a few regions of epididymis. To determine the functional importance of this pathway, we performed pharmacological suppression of Wnt signalling in organ culture system and showed that inhibition of this pathway results in uncoiled epididymis. Next, we developed a novel epididymal specific doxycycline regulated Cre mouse model. In this model, Cre expression is controlled by doxycycline and is limited to the epididymal/Wolffian duct epithelium, but is absent in testis. Using this Cre reporter system, we developed two triple transgenic mouse models with aberrant Wnt signalling in epididymis/Wolffian duct. Examination of epididymis from these mouse models revealed uncoiled ductal epithelium. Collectively, our results have established that a precise regulation of Wnt signalling is essential for epididymal coiling and development.