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CHDs occur in nearly 1% of newborns and in over 5% of fetuses that do not survive to term in the Western world (Hoffman 1995; Hoffman and Kaplan 2002). Due to advances in medicine, there is a growing number of children and adults living with CHDs who require lifelong healthcare (Hoffman and Kaplan 2002). Therefore, understanding the molecular mechanisms of heart development and the underlying causes of CHDs has immediate translational significance. BMP signaling pathways are critical regulators of heart development in species as varied as fruit flies, chickens, mice, and humans. Mutations in the BMP pathway have been identified in humans with CHDs. This review discussed the critical roles of BMP signaling pathways in cardiac specification from the mesoderm, myocardial wall formation, valve development, chamber septation, and outflow tract morphogenesis. Because cardiac morphogenesis and BMP signaling pathways are evolutionarily conserved, information gleaned from a variety of model systems provides valuable insight into human heart development and CHDs. In the future this insight may help develop diagnostic tests

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**5** 

*China* 

**Molecular Mechanisms** 

Jing-bin Huang and Jian Liang

**of Congenital Heart Disease** 

*Department of Cardiothoracic Surgery, The Affiliated Ruikang Hospital of Guangxi Traditional Chinese Medical College, Nanning* 

Congenital heart disease (CHD) is the most common type of birth defect, affecting 1% of all live births, and is the leading non-infectious cause of death in the first year of life [1,2]. CHD is a multifactorial complex disease, with environmental and genetic factors playing important roles. It has been recognized that environmental factors/insults during fetal development increase the risk of CHD, including viral infections with rubella [3], exposure to chemical teratogens such as retinoic acid , lithium, dilantin [4]and halogenated hydrocarbon [5]and maternal diseases including diabetes and systemic lupus erythematosus [1, 6]. Epidemiologic studies of CHD have demonstrated an increased recurrence risk for cardiac malformations in sequent pregnancies, supporting the existence of gene

Great progress in molecular genetics and developmental biology has been made. Current genetic techniques for evaluation of congenital heart defects include cytogenetic techniques, fluorescence in situ hybridization (FISH) and DNA mutation analysis. Most methods employ polymerase chain reaction–based assays. Indirect screening methods, such as denaturing high-performance liquid chromatography or single-strand conformation polymorphism have been used extensively. More expensive exon-by-exon sequencing of genomic DNA has recently emerged [7, 8]. It has been accepted that the intricate process of cardiac morphogenesis is controlled by a network of highly conserved genetic and molecular pathways. The origins of CHD are diverse, such as abnormal chromosome structure (eg. duplication or deletion), gene mutations, single nucleotide polymorphisms,

In humans, heart development begins at 15 to 16 days of gestation with the migration of precardiac stem cells, in five steps:(1)migration of precardiac cells from the primitive streak and assembly of the paired cardiac crescents at the myocardial plate, (2) coalescence of the cardiac crescents to form the primitive heart tube, establishing the definitive heart, (3) cardiac looping, assurance of proper alignment of the future cardiac chambers, (4) septation and heart chambers formation, and (5) development of the cardiac conduction system and coronary vasculature [9-11]. The establishment of left-right asymmetry is very important to the normal development of heart [12, 13]. Secreted FGF, BMP, Nodal, and Wnt act as input signal of symmetric cardiac morphogenesis, BMP2, FGF8, Shh/Ihh, and Nodal function as positive regulators, whereas Wnt and Ser are negative regulators [14-16]. The cardiogenic

abnormal RNA, epigenetics and so on, and they are summarized in Figure 1.

**1. Introduction** 

predispositions.

