Document Detail

Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors.
MedLine Citation:
PMID:  19914233     Owner:  NLM     Status:  MEDLINE    
The fine-tuning of BMP signals is critical for many aspects of complex organogenesis. In this report, we show that the augmentation of BMP signaling by a BMP-binding secreted factor, Crossveinless2 (Cv2), is essential for the early embryonic development of mammalian nephrons. In the Cv2-null mouse, the number of cap condensates (clusters of nephron progenitors, which normally express Cv2) was decreased, and the condensate cells exhibited a reduced level of aggregation. In these Cv2(-/-) condensates, the level of phosphorylated Smad1 (pSmad1) was substantially lowered. The loss of a Bmp7 allele in the Cv2(-/-) mouse enhanced the cap condensate defects and further decreased the level of pSmad1 in this tissue. These observations indicated that Cv2 has a pro-BMP function in early nephrogenesis. Interestingly, the renal defects of the Cv2(-/-) mutant were totally suppressed by a null mutation of Twisted gastrulation (Tsg), which encodes another BMP-binding factor, showing that Cv2 exerts its pro-BMP nephrogenic function Tsg-dependently. By using an embryonic kidney cell line, we presented experimental evidence showing that Cv2 enhances pro-BMP activity of Tsg. These findings revealed the molecular hierarchy between extracellular modifiers that orchestrate local BMP signal peaks in the organogenetic microenvironment.
Makoto Ikeya; Kumi Fukushima; Masako Kawada; Sachiko Onishi; Yasuhide Furuta; Shigenobu Yonemura; Toshio Kitamura; Tetsuya Nosaka; Yoshiki Sasai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-13
Journal Detail:
Title:  Developmental biology     Volume:  337     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-02-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-14     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo, Kobe 650-0047, Japan.
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MeSH Terms
Bone Morphogenetic Protein 7 / metabolism*
Carrier Proteins / metabolism*
Cell Aggregation
Cells, Cultured
Epistasis, Genetic
Kidney Tubules, Collecting / embryology,  metabolism,  pathology
Mutation / genetics
Nephrons / embryology*,  metabolism*,  pathology
Proteins / metabolism*
Signal Transduction
Reg. No./Substance:
0/Bone Morphogenetic Protein 7; 0/Carrier Proteins; 0/Proteins; 0/crossveinless 2 protein, mouse; 0/twisted gastrulation protein, mouse

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