Affiliation:
1. Department of Zoology, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
2. AMED Core Research for Evolutional Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo 100-0004, Japan
Abstract
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 bisexually, 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 the 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 the 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 MD, and also serves as a paradiagmatic example of how an epithelial cell sheet is transformed to a tubular structure, a process seen in a variety of developmental contexts.
Funder
Grant-in-Aid for Scientific Research on Innovative Areas
Grant-in-Aid for challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan
Mitsubishi Foundation
Senshin Medical Research Foundation
Takeda Science Foundation
Naito Foundation
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Cited by
41 articles.
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