Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish.
Dev Biol
; 317(2): 486-96, 2008 May 15.
Article
em En
| MEDLINE
| ID: mdl-18407257
ABSTRACT
NDRG4 is a novel member of the NDRG family (N-myc downstream-regulated gene). The roles of NDRG4 in development have not previously been evaluated. We show that, during zebrafish embryonic development, ndrg4 is expressed exclusively in the embryonic heart, the central nervous system (CNS) and the sensory system. Ndrg4 knockdown in zebrafish embryos causes a marked reduction in proliferative myocytes and results in hypoplastic hearts. This growth defect is associated with cardiac phenotypes in morphogenesis and function, including abnormal heart looping, inefficient circulation and weak contractility. We reveal that ndrg4 is required for restricting the expression of versican and bmp4 to the developing atrioventricular canal. This constellation of ndrg4 cardiac defects phenocopies those seen in mutant hearts of heartstrings (hst), the tbx5 loss-of-function mutants in zebrafish. We further show that ndrg4 expression is significantly decreased in hearts with reduced tbx5 activities. Conversely, increased expression of tbx5 that is due to tbx20 knockdown leads to an increase in ndrg4 expression. Together, our studies reveal an essential role of ndrg4 in regulating proliferation and growth of cardiomyocytes, suggesting that ndrg4 may function downstream of tbx5 during heart development and growth.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Peixe-Zebra
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Proteínas de Peixe-Zebra
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Miócitos Cardíacos
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Proteínas Musculares
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Revista:
Dev Biol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos