The murine homeobox gene Csx/Nkx2.5 is an evolutionarily highly conserved gene related to the Drosophila tinman

The molecular mechanisms which guide development of the heart, in vertebrates and many other species, have been the subject of intense investigation in recent years (Fishman and Chien, 1997; Olson and Srivastava, 1996). These studies have suggested common molecular pathways which are evolutionarily conserved from simpler species such as Drosophila to higher species including mammals (Bodmer and Venkatesh, 1998; Harvey, 1996). This evolutionary conservation is particularly striking, since insects and vertebrates diverged more than 500 million years ago and the heart is quite distinct anatomically in these widely divergent species. In most vertebrates, the heart begins initially as a crescent shaped mesodermal structure located anteriorly and laterally. This precardiac mesoderm is brought ventrally and caudally, by folding of the embryo, to form a single midline heart tube with the inflow region located most caudally and the outflow region located most rostrally. This tube undergoes looping, bringing the inflow, ventricular and outflow regions of the heart into the alignment seen in the mature heart. Later, chamber septation occurs, valves develop in the atrioventricular junction as well as in the outflow tract, and the outflow tract itself is divided into two great vessels. Additional refinements occur with the development of the coronary arteries and the cardiac conduction system (Sadler, 1995). Heart development is governed by complex signals 1439 Development 126, 1439-1450 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV4082