Protein tyrosine kinase 7 is essential for tubular morphogenesis of the Wolffian duct

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dc.contributor.authorXu, Bingfang
dc.contributor.authorWashington, Angela M.
dc.contributor.authorDomeniconi, Raquel Fantin [UNESP]
dc.contributor.authorFerreira Souza, Ana Cláudia
dc.contributor.authorLu, Xiaowei
dc.contributor.authorSutherland, Ann
dc.contributor.authorHinton, Barry T.
dc.contributor.institutionUniversity of Virginia School of Medicine
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionFederal University of Viçosa
dc.date.accessioned2018-12-11T17:27:32Z
dc.date.available2018-12-11T17:27:32Z
dc.date.issued2016-04-15
dc.description.abstractThe Wolffian duct, the proximal end of the mesonephric duct, undergoes non-branching morphogenesis to achieve an optimal length and size for sperm maturation. It is important to examine the mechanisms by which the developing mouse Wolffian duct elongates and coils for without proper morphogenesis, male infertility will result. Here we show that highly proliferative epithelial cells divide in a random orientation relative to the elongation axis in the developing Wolffian duct. Convergent extension (CE)-like of cell rearrangements is required for elongating the duct while maintaining a relatively unchanged duct diameter. The Wolffian duct epithelium is planar polarized, which is characterized by oriented cell elongation, oriented cell rearrangements, and polarized activity of regulatory light chain of myosin II. Conditional deletion of protein tyrosine kinase 7 (PTK7), a regulator of planar cell polarity (PCP), from mesoderm results in loss of the PCP characteristics in the Wolffian duct epithelium. Although loss of Ptk7 does not alter cell proliferation or division orientation, it affects CE and leads to the duct with significantly shortened length, increased diameter, and reduced coiling, which eventually results in loss of sperm motility, a key component of sperm maturation. In vitro experiments utilizing inhibitors of myosin II results in reduced elongation and coiling, similar to the phenotype of Ptk7 knockout. This data suggest that PTK7 signaling through myosin II regulates PCP, which in turn ensures CE-like of cell rearrangements to drive elongation and coiling of the Wolffian duct. Therefore, PTK7 is essential for Wolffian duct morphogenesis and male fertility.en
dc.description.affiliationDepartment of Cell Biology University of Virginia School of Medicine
dc.description.affiliationDepartment of Anatomy Institute of Biosciences – UNESP
dc.description.affiliationDepartment of General Biology Federal University of Viçosa
dc.description.affiliationUnespDepartment of Anatomy Institute of Biosciences – UNESP
dc.format.extent219-233
dc.identifierhttp://dx.doi.org/10.1016/j.ydbio.2016.02.029
dc.identifier.citationDevelopmental Biology, v. 412, n. 2, p. 219-233, 2016.
dc.identifier.doi10.1016/j.ydbio.2016.02.029
dc.identifier.file2-s2.0-84960969698.pdf
dc.identifier.issn1095-564X
dc.identifier.issn0012-1606
dc.identifier.lattes5481756528299469
dc.identifier.orcid0000-0003-2938-010X
dc.identifier.scopus2-s2.0-84960969698
dc.identifier.urihttp://hdl.handle.net/11449/177880
dc.language.isoeng
dc.relation.ispartofDevelopmental Biology
dc.relation.ispartofsjr2,087
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectMale infertility
dc.subjectPlanar cell polarity
dc.subjectPtk7
dc.subjectTubular morphogenesis
dc.subjectWolffian duct
dc.titleProtein tyrosine kinase 7 is essential for tubular morphogenesis of the Wolffian ducten
dc.typeArtigo
unesp.author.lattes5481756528299469[3]
unesp.author.orcid0000-0003-2938-010X[3]

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