AbstractHeart development is an evolutionarily conserved process. The cardiac organ of Drosophila melanogaster is the dorsal vessel, a linear contractile tissue with cellular and morphogenetic similarities to the primitive heart tube formed at an early stage of vertebrate heart formation. Abundant evidence shows comparable intercellular signaling pathways and transcription factor networks are utilized in Drosophila and vertebrates, to specify cardiac progenitor cells and instruct their differentiation and function in forming the mature heart. With this proven conservation in mind, we screened the second chromosome of Drosophila for genetic intervals that harbor additional loci required for normal dorsal vessel morphogenesis. Our studies identified numerous regions, that when deleted, culminated in dorsal vessels with abnormal cell numbers and/or structural properties. Certain of the deficiency intervals were further characterized to identify individual genes essential for proper cardiac organ formation. Our analyses identified eight genes of diverse functions that are needed for dorsal vessel development. Several of these sequences have known vertebrate homologues, further supporting a conserved genetic basis for heart formation in Drosophila and higher eukaryotes. genesis 45:607–617, 2007. © 2007 Wiley‐Liss, Inc.