Atrial natriuretic factor in the developing heart: a signpost for cardiac morphogenesis

2011 ◽  
Vol 89 (8) ◽  
pp. 533-537 ◽  
Author(s):  
Benoit G. Bruneau

The developing heart forms during the early stages of embryogenesis, and misregulated heart development results in congenital heart defects (CHDs). To understand the molecular basis of CHDs, a deep understanding of the morphological and genetic basis of heart development is necessary. Atrial Natriuretic Factor (ANF) is an important and extremely sensitive marker for specific regions of the developing heart, as well as for disturbances in the patterning of the heart. This review summarizes the dynamic expression of ANF in the developing heart and its usefulness in understanding the early molecular defects underlying CHDs.

2004 ◽  
Vol 24 (23) ◽  
pp. 10151-10160 ◽  
Author(s):  
Tae-gyun Kim ◽  
Junqin Chen ◽  
Junich Sadoshima ◽  
Youngsook Lee

ABSTRACT Mice with a homozygous knockout of the jumonji (jmj) gene showed abnormal heart development and defective regulation of cardiac-specific genes, including the atrial natriuretic factor (ANF). ANF is one of the earliest markers of cardiac differentiation and a hallmark for cardiac hypertrophy. Here, we show that JMJ represses ANF gene expression by inhibiting transcriptional activities of Nkx2.5 and GATA4. JMJ represses the Nkx2.5- or GATA4-dependent activation of the reporter genes containing the ANF promoter-enhancer or containing the Nkx2.5 or GATA4-binding consensus sequence. JMJ physically associates with Nkx2.5 and GATA4 in vitro and in vivo as determined by glutathione S-transferase pull-down and immunoprecipitation assays. Using mutational analyses, we mapped the protein-protein interaction domains in JMJ, Nkx2.5, and GATA4. We identified two DNA-binding sites of JMJ in the ANF enhancer by gel mobility shift assays. However, these JMJ-binding sites do not seem to mediate ANF repression by JMJ. Mutational analysis of JMJ indicates that the protein-protein interaction domain of JMJ mediates the repression of ANF gene expression. Therefore, JMJ may play important roles in the down-regulation of ANF gene expression and in heart development.


1996 ◽  
Vol 16 (9) ◽  
pp. 4648-4655 ◽  
Author(s):  
D Durocher ◽  
C Y Chen ◽  
A Ardati ◽  
R J Schwartz ◽  
M Nemer

The recently described NK2 family of homeodomain proteins are key developmental regulators. In Drosophila melanogaster, two members of this family, bagpipe and tinman, are required for visceral and cardiac mesoderm formation, respectively. In vertebrates, tinman appears to represent a family of closely related NK2 genes, including Nkx-2.5, that are expressed at an early stage in precardiac cells. Consistent with a role for Nkx-2.5 in heart development, inactivation of the Nkx-2.5 gene in mice causes severe cardiac malformations and embryonic lethality. However, little is known about the molecular action of Nkx-2.5 and its targets in cardiac muscle. In this paper, we report the identification and characterization of a functional and highly conserved Nkx-2.5 response element, termed the NKE, in the proximal region of the cardiac atrial natriuretic factor (ANF) promoter. The NKE is composed of two near-consensus NK2 binding sites that are each able to bind purified Nkx-2.5. The NKE is sufficient to confer cardiac cell-specific activity to a minimal TATA-containing promoter and is required for Nkx-2.5 activation of the ANF promoter in heterologous cells. Interestingly, in primary cardiocyte cultures, the NKE contributes to ANF promoter activity in a chamber- and developmental stage-specific manner, suggesting that Nkx-2.5 and/or other related cardiac proteins may play a role in chamber specification. This work provides the identification of a direct target for NK2 homeoproteins in the heart and lays the foundation for further molecular analyses of the role of Nkx-2.5 and other NK2 proteins in cardiac development.


1987 ◽  
Vol 16 (1) ◽  
pp. 63-77 ◽  
Author(s):  
John W. Jacobs ◽  
George P. Vlasuk ◽  
Michael Rosenblatt

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S165-S166 ◽  
Author(s):  
G. WAMBACH ◽  
S. GÖTZ ◽  
G. SUCKAU ◽  
G. BÖNNER ◽  
W. KAUFMANN

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