The primitive linear heart tube (dorsal vessel) of the fruit fly Drosophila melanogaster provides a unique model system to study the genetic control mechanisms of the heart development. Although during last decade studies of cardiac morphogenesis using model animal systems identified important genes for cardiac development, many cardiogenic genes remain to be identified in order to gain insight into the genetic control mechanism of cardiac morphogenesis. Using information obtained Drosophila genome sequencing and RNAi (RNA interference) technology as a new strategy for blocking gene function we performed genome-wide screening of regulatory genes that are involved in the Drosophila heart development. For the screen, we have injected dsRNA into embryos from transgenic flies that harbor beta-galactosidase transgene that is mainly expressed in cells of cardiogenic lineage. By monitoring change in expression pattern of beta-galactosidase transgene and morphology of the heart in the injected embryos we could easily identify potential cardiogenic genes. We have screened over 8,500 Drosophila genes and discovered many genes (total 155 genes) that potentially play roles in Drosophila cardiac development. From this screen, both novel genes and known genes with mammalian homologues and with previously undescribed functions in heart development have been identified. In addition, genes encoding transcription factors and signaling molecules that are involved in known signaling pathways including the Wnt signaling pathway have been identified. Characterizations of those cardiogenic genes are now under way by using both transgenic fly lines that we have generated and potential mutants for the identified genes. Among candidate genes, we found that the simjang gene which encodes a chromatin-remodeling factor is crutial for specification of a subset of cardiac cells. Also, we found that the sprite gene, which encodes a protein containing a PDZ domain, is required for the maturation of the heart tube at late step. Because the genetic control mechanisms of the embryonic cardiac development of the Drosophila are well conserved in mammalian heart development, identifying cardiogenic regulatory genes in Drosophila should help us understand the genetic control mechanism of the mammalian cardiac morphogenesis.
| Kim, Yong-Ou; Park, Sang-Joon; Balaban, Robert S et al. (2004) A functional genomic screen for cardiogenic genes using RNA interference in developing Drosophila embryos. Proc Natl Acad Sci U S A 101:159-64 |
