Genetic dissection of cardiac growth control pathways

Cardiac muscle cells exhibit two related brit distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapi dly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hy perplastic to hypertrophic. Much research has focused on identifying the ca ndidate mitogens, hypertrophic agonists, and signaling pathways that mediat e these processes in isolated cells. What drives the proliferative growth o f embryonic myocardium in vivo and the mechanisms by which adult cardiac my ocytes hypertrophy in vivo are less clear. Efforts to answer these question s have benefited from rapid progress made in techniques to manipulate the m urine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in t he intact heart. These studies have confirmed the importance of suspected p athways, have implicated unexpected pathways as well, and have led to new p aradigms for the control of cardiac growth.