Fstl1 antagonizes BMP signaling and regulates ureter development.

Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in deve...

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Autores principales:	Jingyue Xu, Xin Qi, Jianfeng Gong, Mingyan Yu, Fangxiong Zhang, Haibo Sha, Xiang Gao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1fe5c222c0da4ffc87b9aba407c4e3c3
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spelling	oai:doaj.org-article:1fe5c222c0da4ffc87b9aba407c4e3c32021-11-18T07:23:31ZFstl1 antagonizes BMP signaling and regulates ureter development.1932-620310.1371/journal.pone.0032554https://doaj.org/article/1fe5c222c0da4ffc87b9aba407c4e3c32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22485132/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activity. Mouse embryos carrying disrupted Fstl1 gene displayed prominent hydroureter arising from proximal segment and ureterovesical junction defects. These defects were associated with significant reduction in ureteric epithelial cell proliferation at E15.5 and E16.5 as well as absence of subepithelial ureteral mesenchymal cells in the urinary tract at E16.5 and E18.5. At the molecular level, increased BMP signaling was found in Fstl1 deficient ureters, indicated by elevated pSmad1/5/8 activity. In vitro study also indicated that Fstl1 can directly bind to ALK6 which is specifically expressed in ureteric epithelial cells in developing ureter. Furthermore, Sonic hedgehog (SHH) signaling, which is crucial for differentiation of ureteral subepithelial cell proliferation, was also impaired in Fstl1(-/-) ureter. Altogether, our data suggest that Fstl1 is essential in maintaining normal ureter development by antagonizing BMP signaling.Jingyue XuXin QiJianfeng GongMingyan YuFangxiong ZhangHaibo ShaXiang GaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e32554 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jingyue Xu Xin Qi Jianfeng Gong Mingyan Yu Fangxiong Zhang Haibo Sha Xiang Gao Fstl1 antagonizes BMP signaling and regulates ureter development.
description	Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activity. Mouse embryos carrying disrupted Fstl1 gene displayed prominent hydroureter arising from proximal segment and ureterovesical junction defects. These defects were associated with significant reduction in ureteric epithelial cell proliferation at E15.5 and E16.5 as well as absence of subepithelial ureteral mesenchymal cells in the urinary tract at E16.5 and E18.5. At the molecular level, increased BMP signaling was found in Fstl1 deficient ureters, indicated by elevated pSmad1/5/8 activity. In vitro study also indicated that Fstl1 can directly bind to ALK6 which is specifically expressed in ureteric epithelial cells in developing ureter. Furthermore, Sonic hedgehog (SHH) signaling, which is crucial for differentiation of ureteral subepithelial cell proliferation, was also impaired in Fstl1(-/-) ureter. Altogether, our data suggest that Fstl1 is essential in maintaining normal ureter development by antagonizing BMP signaling.
format	article
author	Jingyue Xu Xin Qi Jianfeng Gong Mingyan Yu Fangxiong Zhang Haibo Sha Xiang Gao
author_facet	Jingyue Xu Xin Qi Jianfeng Gong Mingyan Yu Fangxiong Zhang Haibo Sha Xiang Gao
author_sort	Jingyue Xu
title	Fstl1 antagonizes BMP signaling and regulates ureter development.
title_short	Fstl1 antagonizes BMP signaling and regulates ureter development.
title_full	Fstl1 antagonizes BMP signaling and regulates ureter development.
title_fullStr	Fstl1 antagonizes BMP signaling and regulates ureter development.
title_full_unstemmed	Fstl1 antagonizes BMP signaling and regulates ureter development.
title_sort	fstl1 antagonizes bmp signaling and regulates ureter development.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1fe5c222c0da4ffc87b9aba407c4e3c3
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_version_	1718423521024016384

Fstl1 antagonizes BMP signaling and regulates ureter development.

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