BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis.
Dev Biol
; 315(2): 383-96, 2008 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-18261719
ABSTRACT
Atrioventricular (AV) endocardium transforms into the cushion mesenchyme, the primordia of the valves and membranous septa, through epithelial-mesenchymal transformation (EMT). While bone morphogenetic protein (BMP)-2 is known to be critical for AV EMT, the role of BMP-2 in post-EMT AV valvulogenesis remains to be elucidated. To find BMP signaling loops, we first localized Type I BMP receptors (BMPRs), BMPR-1A (ALK3), -1B (ALK6) and ALK2 in AV cushion mesenchyme in stage-24 chick embryos. Based on the BMP receptor expression pattern, we examined the functional roles of BMP-2 and BMP signaling in post-EMT valvulogenesis by using stage-24 AV cushion mesenchymal cell aggregates cultured on 3D-collagen gels. Exogenous BMP-2 or constitutively active (ca) BMPR-1B (ALK6)-virus treatments induced migration of the mesenchymal cells into the collagen gels, whereas noggin, an antagonist of BMPs, or dominant-negative (dn) BMPR-1 B (ALK6)-virus treatments reduced cell migration from the mesenchymal cell aggregates. Exogenous BMP-2 or caBMPR-1B (ALK6) treatments significantly promoted expression of an extracellular matrix (ECM) protein, periostin, a known valvulogenic matrix maturation mediator, at both mRNA and protein levels, whereas periostin expression was repressed by adding noggin or dnBMPR-1B (ALK6)-virus to the culture. Moreover, transcripts of Twist and Id1, which have been implicated in cell migration in embryogenesis and activation of the periostin promoter, were induced by BMP-2 but repressed by noggin in cushion mesenchymal cell cultures. These data provide evidence that BMP-2 and BMP signaling induce biological processes involved in early AV valvulogenesis, i.e. mesenchymal cell migration and expression of periostin, indicating critical roles for BMP signaling in post-EMT AV cushion tissue maturation and differentiation.
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Base de dados:
MEDLINE
Assunto principal:
Moléculas de Adesão Celular
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Fator de Crescimento Transformador beta
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Proteínas Morfogenéticas Ósseas
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Coxins Endocárdicos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article