Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development

• Published in: Developmental biology Vol. 400; no. 1; pp. 139 - 147
• Main Authors: Okazawa, Mika, Murashima, Aki, Harada, Masayo, Nakagata, Naomi, Noguchi, Masafumi, Morimoto, Mitsuru, Kimura, Tadashi, Ornitz, David M., Yamada, Gen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2015
• Subjects: Animals; Cell proliferation; Cell Proliferation - physiology; Epithelium - metabolism; Fgfr; Gene Expression Regulation, Developmental - physiology; Histological Techniques; Immunohistochemistry; In Situ Hybridization; Male; Mice; Models, Genetic; Receptor tyrosine kinase; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Ret; Signal Transduction - physiology; Ureteric bud; Wolffian duct; Wolffian Ducts - embryology; Ret; Cell proliferation; Receptor tyrosine kinase; Ureteric bud; Fgfr; Wolffian duct
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2015.01.023

The Wolffian duct (WD) is a primordium of the male reproductive tract and kidney collecting duct system. Fibroblast growth factor receptors (FGFRs), members of the receptor tyrosine kinase (RTK) family, are essential for kidney development. Although the functions of FGFR signaling in kidney morphogenesis have been analyzed, their function in WD development has not been comprehensively investigated. Here, we demonstrate that Fgfr2 is the major Fgfr gene expressed throughout the WD epithelia and that it is essential for the maintenance of the WD, specifically in the caudal part of the WD. Hoxb7-Cre mediated inactivation of Fgfr2 in the mouse WD epithelia resulted in the regression of the caudal part of the WD and abnormal male reproductive tract development. Cell proliferation and expression of the downstream target genes of RTK signaling (Etv4 and Etv5) were decreased in the caudal part of the WD epithelia in the mutant embryos. Cranial (rostral) WD formation and ureteric budding were not affected. Ret, Etv4, and Etv5 expression were sustained in the ureteric bud of the mutant embryos. Taken together, these data suggest region-specific requirements for FGFR2 signaling in the developing caudal WD epithelia. [Display omitted] •Fgfr2 is the major Fgfr gene expressed in the Wolffian duct (WD) epithelia.•WD-specific inactivation of Fgfr2 results in ductal regression in the caudal WD.•FGFR signaling regulates cell proliferation in the caudal WD.•WD-epithelial cell proliferation may be regulated by region-specific mechanisms.