Bmp7 functions via a polarity mechanism to promote cloacal septation.

<h4>Background</h4>During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and presen...

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Autores principales: Kun Xu, Xinyu Wu, Ellen Shapiro, Honging Huang, Lixia Zhang, Duane Hickling, Yan Deng, Peng Lee, Juan Li, Herbert Lepor, Irina Grishina
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:72f5ea658f0249998899d634e31723ec2021-11-18T07:30:18ZBmp7 functions via a polarity mechanism to promote cloacal septation.1932-620310.1371/journal.pone.0029372https://doaj.org/article/72f5ea658f0249998899d634e31723ec2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253716/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.<h4>Methodology/principal findings</h4>We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.<h4>Conclusion/significance</h4>Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations.Kun XuXinyu WuEllen ShapiroHonging HuangLixia ZhangDuane HicklingYan DengPeng LeeJuan LiHerbert LeporIrina GrishinaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29372 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kun Xu
Xinyu Wu
Ellen Shapiro
Honging Huang
Lixia Zhang
Duane Hickling
Yan Deng
Peng Lee
Juan Li
Herbert Lepor
Irina Grishina
Bmp7 functions via a polarity mechanism to promote cloacal septation.
description <h4>Background</h4>During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.<h4>Methodology/principal findings</h4>We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.<h4>Conclusion/significance</h4>Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations.
format article
author Kun Xu
Xinyu Wu
Ellen Shapiro
Honging Huang
Lixia Zhang
Duane Hickling
Yan Deng
Peng Lee
Juan Li
Herbert Lepor
Irina Grishina
author_facet Kun Xu
Xinyu Wu
Ellen Shapiro
Honging Huang
Lixia Zhang
Duane Hickling
Yan Deng
Peng Lee
Juan Li
Herbert Lepor
Irina Grishina
author_sort Kun Xu
title Bmp7 functions via a polarity mechanism to promote cloacal septation.
title_short Bmp7 functions via a polarity mechanism to promote cloacal septation.
title_full Bmp7 functions via a polarity mechanism to promote cloacal septation.
title_fullStr Bmp7 functions via a polarity mechanism to promote cloacal septation.
title_full_unstemmed Bmp7 functions via a polarity mechanism to promote cloacal septation.
title_sort bmp7 functions via a polarity mechanism to promote cloacal septation.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/72f5ea658f0249998899d634e31723ec
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