Semin Neonato11999; 4:125-130 Early events of cardiovascular development Thomas A. Drysdale Lawson Research Institute, 268 Grosvenor St., London, Ontario, Canada, N6A 4V2, and Depts. of Paediatrics and Physiology University of Western Ontario London, Ontario, Canada Key words: cardiogenesis, congenital heart disease, left-right asymmetry, homeobox, organogenesis A number of mutations that give rise to familial cardiac disease have been discovered and these now include some specific mutations that can account for a subset of congenital heart defects. It is now possible to identify individuals that carry the disease in affected families and provide therapy to those individuals. Embryological studies have discovered novel genes that are likely to play significant roles in cardiogenesis and in the establishment of left-right asymmetry. Analysis of these early events in cardiogenesis will undoubtedly lead to a better understanding of the causes of congenital heart defects that affect the neonate. Early events in cardiovascular development Despite cardiovascular development's long history (chick cardiovascular development was looked at by Aristotle [1]), our understanding of cardiovascular development has not contributed substantially to our understanding of cardiovascular disease in the neonate. This is unfortunate, since almost 1% of all live births have cardiac malformations and cardiac malformations may represent a significant cause of spontaneous abortions [2]. Until recently, our understanding of cardiac development was pri- marily restricted to careful morphological obser- vations on the mechanisms that transform the heart from a simple tube to the complex, multi- chambered structure required for life. Molecular insights into cardiac development were restricted to our knowledge of cardiac-specific isoforms of con- tractile proteins and how they were regulated. Although important work, it did little to further our understanding of congenital defects. This infor- mation is limiting, because in order to understand how the heart is formed in the embryo, it is essen- tial to understand the cellular movements and inter- actions that are needed for heart formation. This is Correspondence: Thomas A. Drysdale, Lawson Research Institute. Tel: 519 646--6100 (ext. 64675); Fax: 519 646-6110; emall: tdrysdale(~lrl.stjosephs.london.on.ca 1084-27561991020125+06 $12.00•0 the domain of classical embryology studies. It is also important to understand the molecules that mediate the interactions and direct differentiation. This is the domain of molecular biology. In iso- lation, neither of these fields of study will provide a complete picture of how a heart is formed. There is currently a renewed focus on cardiovas- cular development. The tools of molecular embry- ology have been applied to an array of model organisms that each have properties that make them useful for studying the heart. This intensive research appears to have advanced our knowledge to the point that many of the novel findings in cardiac development have direct clinical relevance. These advances have primarily come in two areas. First, studies of families with heritable cardiovascu- lar disease have identified mutations in a number of genes that result in the disease state. Second, the application of molecular biology to well under- stood embryological models has resulted in the discovery of a number of novel genes that appear to be key players in cardiovascular development. Mutations that result in cardiovascular disease When a hereditary cardiac defect is found :i~ ~a family it provides an opportunity to del:~e, ~he © 1999 Harcourt Publishers Ltd