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• W2034994597 abstract "You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2011255 MESENCHYMAL SIGNAL PROMOTES TOPOLOGICAL SEPARATION OF THE URETHRAL AND RECTAL COMPARTMENTS. INSIGHTS INTO THE HUMAN CLOACAL SYNDROMES Xinyu Wu, Kun Xu, Ellen Shapiro, Herbert Lepor, and Irina Grishina Xinyu WuXinyu Wu New York, NY More articles by this author , Kun XuKun Xu New York, NY More articles by this author , Ellen ShapiroEllen Shapiro New York, NY More articles by this author , Herbert LeporHerbert Lepor New York, NY More articles by this author , and Irina GrishinaIrina Grishina New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.346AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Defects in separation of the urethral and hindgut compartments result in congenital malformations such as persistent cloaca and rectourethral fistulas in about 1:50,000 live human births. Loss of the homeobox genes Hoxa,d13 and developmental signaling molecules, such as Sonic hedgehog and Bone morphogenetic protein 7 (BMP7) in mouse models result in recto-urethral fistulas and genital malformations. However, the cellular mechanisms of cloacal development are still not understood. The objective of this study is to test a hypothesis that cloacal partitioning is driven by a BMP7 signal from the cloacal mesenchyme to promote topological separation of the urethral and hingut epithelium by favoring apical–basal polarity of cell divisions in the cloacal endoderm. METHODS We analyzed cloacal development from embryonic day 10.5 to 13.5 in Bmp7 null mutants and normal wild type and heterozygous littermates. We performed immunofluorescent analysis of paraffin tissue sections, and Western analysis of the cloacal region, to determine the effect of loss of Bmp7 on cell proliferation, apoptosis, epithelial differentiation, adhesion and polarity of cell divisions in the cloacal endoderm and adjacent mesenchyme. Distributions of mitotic angles in the cloacal endoderm were determined by immunofluorescent labeling of the mitotic chromosomes with phospho-histone H3, confocal imaging of transverse cloacal z-sections, and analysis using Volocity software. Statistical significance was determined by the two-sample Kolmogorov-Smirnov test. RESULTS We report that that in mid-embryogenesis BMP7 signaling from the urorectal mesenchyme promotes dorsal-ventral patterning of the cloacal endoderm by limiting accumulation of LEF1, a component of the WNT signaling, to the rectal compartment. We further show that BMP7 promotes activation of the Jun N-terminal kinases, and cell proliferation in the cloacal region. BPM7 also promoted cell survival, expression of cytokeratin 14 and apical-basal polarity of cell divisions in the cloacal endoderm. CONCLUSIONS Our studies provide a substantial evidence that cloacal partitioning is driven by the mesenchymal signal to promote survival and reorganization of the endodermal epithelium. These results provide a novel insight into the mechanisms of cloacal development, and the possible genetic and cellular causes for the human cloacal syndromes. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e102-e103 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Xinyu Wu New York, NY More articles by this author Kun Xu New York, NY More articles by this author Ellen Shapiro New York, NY More articles by this author Herbert Lepor New York, NY More articles by this author Irina Grishina New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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