Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors.
Dev Biol
; 337(2): 405-14, 2010 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-19914233
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Proteínas de Transporte
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Proteína Morfogenética Óssea 7
/
Néfrons
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article