The Müllerian duct (MD) and Wolffian duct (WD) are embryonic tubular tissues giving rise to female and male reproductive tracts, respectively. In amniote embryos, both MD and WD emerge in both sexes, but subsequently degenerate in the males and females, respectively. Here, by using MD-specific gene manipulations in chicken embryos, we identify the molecular and cellular mechanisms that link early MD specification to tubular invagination. Early (pre-)specification of MD precursors in the coelomic epithelium requires BMP signaling and its downstream target Pax2 in a WD-independent process. Subsequently, the BMP/Pax2 axis induces Lim1 expression, a hallmark of MD specification, for which FGF/ERK and WD-derived signals are also required. Finally, the sequential actions of the BMP/Pax2 and FGF/Lim1 axes culminate in epithelial invagination to form a tubular structure driven by an apical constriction, where apical accumulation of phospho-myosin light chain is positively regulated by FGF/ERK signaling. Our study delineates mechanisms governing the early formation of the MD, and also serves as a model of how an epithelial cell sheet is transformed to a tubular structure, a process seen in a variety of developmental contexts.
The authors declare no competing or financial interests.
Conceptualization: Y.A.; Methodology: Y.A.; Formal analysis and investigation: Y.A.; Writing - original draft preparation: Y.A.; Writing - review and editing: Y.A. and Y.T.; Funding acquisition: Y.A. and Y.T.
This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas, and a Grant-in-Aid for Challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); the Mitsubishi Foundation; the Senshin Medical Research Foundation; and the Takeda Science Foundation. Y.A. is the recipient of a fellowship from the Naito Foundation.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.137067.supplemental
- Received March 14, 2016.
- Accepted August 4, 2016.