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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2011-3-7
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pubmed:abstractText |
Urinary tract morphogenesis requires subdivision of the ureteric bud (UB) into the intra-renal collecting system and the extra-renal ureter, by responding to signals in its surrounding mesenchyme. BMP4 is a mesenchymal regulator promoting ureter development, while GREM1 is necessary to negatively regulate BMP4 activity to induce UB branching. However, the mechanisms that regulate the GREM1-BMP4 signaling are unknown. Previous studies have shown that Six1-deficient mice lack kidneys, but form ureters. Here, we show that the tip cells of Six1(-/-) UB fail to form an ampulla for branching. Instead, the UB elongates within Tbx18- and Bmp4-expressing mesenchyme. We find that the expression of Grem1 in the metanephric mesenchyme (MM) is Six1-dependent. Treatment of Six1(-/-) kidney rudiments with GREM1 protein restores ampulla formation and branching morphogenesis. Furthermore, we demonstrate that genetic reduction of BMP4 levels in Six1(-/-) (Six1(-/-); Bmp4(+/-)) embryos restores urinary tract morphogenesis and kidney formation. This study uncovers an essential function for Six1 in the MM as an upstream regulator of Grem1 in initiating branching morphogenesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Grem1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Six1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/T-Box Domain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tbx18 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt11 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1095-564X
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
352
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
141-51
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pubmed:dateRevised |
2011-6-14
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pubmed:meshHeading |
pubmed-meshheading:21281623-Animals,
pubmed-meshheading:21281623-Bone Morphogenetic Protein 4,
pubmed-meshheading:21281623-Embryo, Mammalian,
pubmed-meshheading:21281623-Gene Dosage,
pubmed-meshheading:21281623-Gene Expression Regulation, Developmental,
pubmed-meshheading:21281623-Gene Silencing,
pubmed-meshheading:21281623-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:21281623-Homeodomain Proteins,
pubmed-meshheading:21281623-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:21281623-Kidney,
pubmed-meshheading:21281623-Mesoderm,
pubmed-meshheading:21281623-Mice,
pubmed-meshheading:21281623-Morphogenesis,
pubmed-meshheading:21281623-Organogenesis,
pubmed-meshheading:21281623-Recombinant Proteins,
pubmed-meshheading:21281623-T-Box Domain Proteins,
pubmed-meshheading:21281623-Up-Regulation,
pubmed-meshheading:21281623-Ureter,
pubmed-meshheading:21281623-Wnt Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis.
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pubmed:affiliation |
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of NYU, New York, NY 10029, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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