MUTATIONS AFFECTING THE FORMATION AND FUNCTION OF THE CARDIOVASCULAR-SYSTEM IN THE ZEBRAFISH EMBRYO

As part of a large-scale mutagenesis screen of the zebrafish genome, w e have identified 58 mutations that affect the formation and function of the cardiovascular system, The cardiovascular system is particularl y amenable for screening in the transparent zebrafish embryo because t he heart and blood vessels are prominent and their function easily exa mined, We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function, Nine mutation s clearly disrupt the formation of the heart, cloche deletes the endoc ardium, In cloche mutants, the myocardial layer forms in the absence o f the endocardium but is dysmorphic and exhibits a weak contractility, Two loci, miles apart and bonnie and clyde, play a critical role in t he fusion of the bilateral tubular primordia, Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dy smorphic heart, We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as in dicated by hemorrhage at particular sites, In terms of cardiac functio n, one large group exhibits a weak beat, In this group, five loci affe ct both chambers and seven a specific chamber (the atrium or ventricle ). For example, the weak atrium mutation exhibits an atrium that becom es silent but has a normally beating ventricle, Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrilla ting pattern or an apparent block to conduction, In several other muta nts, regurgitation of blood how from ventricle to atrium is the most p rominent abnormality, due either to the absence of valves or to poor c oordination between the chambers with regard to the timing of contract ion, The mutations identified in this screen point to discrete and cri tical steps in the formation and function of the heart and vasculature .