title: Epithelial Wnt/βcatenin signalling is essential for epididymal coiling.
abstract: Organ shape and size are important determinants of their physiological functions. Epithelial tubes are anlagen of many complex organs. How these tubes acquire their complex shape and size is a fundamental question in biology. In male mice, the Wolffian duct (WD; postnatally known as epididymis) undergoes an astonishing transformation, where a straight tube only a few millimetres long elongates to over 1000 times its original length and fits into a very small space, due to extensive coiling of epithelium, to perform the highly specialized function of sperm maturation. Defective coiling disrupts sperm maturation and leads to male infertility. Recent work has shown that epithelial cell proliferation is a major driver of WD coiling. Still, very little is known about the molecular signals involved in this process. Testicular androgens are known regulators of WD development. However, epithelial androgen receptor signalling is dispensable for WD coiling. In this study, we have shown that Wnt signalling is highly active in the entire WD epithelium during its coiling, and is limited to only a few segments of the epididymis in later life. Pharmacological and genetic suppression of Wnt signalling inhibited WD coiling by decreasing cell proliferation and promoting apoptosis. Comparative gene expression analysis identified Fibroblast growth factor 7 (Fgf7) as a prime Wnt target gene involved in WD coiling and in vitro treatment with Fgf7 protein increased coiling of WDs. In summary, our work has established that epithelial canonical Wnt signalling is a critical regulator of WD coiling and its precise regulation is essential for WD/epididymal differentiation.
authors.affiliation: Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Shafiq M
authors.initials: SM
authors.lastname: Syed
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.affiliation: Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia. Electronic address: pradeep.tanwar@newcastle.edu.au.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Tanwar
mesh_terms: D000818:Animals; D004822:Epididymis / Q000196:embryology / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000235:genetics*; D014928:Wolffian Ducts / Q000196:embryology / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C496454:Fgf7 protein, mouse; D051176:beta Catenin; D051523:Fibroblast Growth Factor 7
keywords: Epididymis; Fertility; Testis; Wnt; Wolffian duct; βcatenin