Understanding heart development and congenital heart defects through developmental biology: a segmental approach.
ABSTRACT The heart is the first organ to form and function during development. In the pregastrula chick embryo, cells contributing to the heart are found in the postero-lateral epiblast. During the pregastrula stages, interaction between the posterior epiblast and hypoblast is required for the anterior lateral plate mesoderm (ALM) to form, from which the heart will later develop. This tissue interaction is replaced by an Activin-like signal in culture. During gastrulation, the ALM is committed to the heart lineage by endoderm-secreted BMP and subsequently differentiates into cardiomyocyte. The right and left precardiac mesoderms migrate toward the ventral midline to form the beating primitive heart tube. Then, the heart tube generates a right-side bend, and the d-loop and presumptive heart segments begin to appear segmentally: outflow tract (OT), right ventricle, left ventricle, atrioventricular (AV) canal, atrium and sinus venosus. T-box transcription factors are involved in the formation of the heart segments: Tbx5 identifies the left ventricle and Tbx20 the right ventricle. After the formation of the heart segments, endothelial cells in the OT and AV regions transform into mesenchyme and generate valvuloseptal endocardial cushion tissue. This phenomenon is called endocardial EMT (epithelial-mesenchymal transformation) and is regulated mainly by BMP and TGFbeta. Finally, heart septa that have developed in the OT, ventricle, AV canal and atrium come into alignment and fuse, resulting in the completion of the four-chambered heart. Altered development seen in the cardiogenetic process is involved in the pathogenesis of congenital heart defects. Therefore, understanding the molecular nature regulating the 'nodal point' during heart development is important in order to understand the etiology of congenital heart defects, as well as normal heart development.
Sakabe
Masahide
M
Department of Anatomy, Graduate School of Medicine, Osaka City University, Abenoku, Osaka, Japan.
Matsui
Hiroko
H
Sakata
Hirokazu
H
Ando
Katsumi
K
Yamagishi
Toshiyuki
T
Nakajima
Yuji
Y
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology; D008648:Mesoderm / Q000502:physiology; D038081:Organogenesis; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D020825:T-Box Domain Proteins; D042461:Vascular Endothelial Growth Factor A