Developmental biology of the heart: molecular understanding morphogenesis, malformations and regenerative medicine

Abstract

Heart is the first organ to form and function during development. At blastula stage, cells that contribute to the cardiogensis are found in the posterior region of the epiblast, and they are specified to the mesoderm fate during gastrula- tion. At gastrula to neurula stages, heart-forming mesoderm in the anterior lateral plate is specified and differentiates to beating primitive heart tube. Subsequently, primitive heart tube establishes an S-shaped heart (d-loop heart). Endocardial cushion tissue, a primordium of valves and septa, is established in atrioventricular canal and outflow tract regions. Thereaf- ter, outflow septum, muscular septum, atrioventricular septum and atrial septum develop individually and align each other, resulting in the formation of four-chambered heart at late embryonic stage. Several genes are identified to regulate these complicated heart forming processes, and candidate genes for human congenital malformation syndromes associated with congenital heart defects are identified, Tbx5 for Holt-Oram syndrome and Tbxl for del22q11 syndrome. Recently, different types of stem cell, which can trans-differentiate to beating cardiomyocytes, are found in adult bone marrow and heart. Understanding the molecular mechanisms of heart development facilitates the stem cell technology that has potential ability to restore heart diseases including congenital heart defects and degenerated heart diseases.