Compared to early heart morphogenesis, the specification of various heart cell types is less well understood. In tinman mutants all the different heart cells are absent, suggesting that tin is essential for heart development and the diversification of different cardiac cells. It is believed that tin might interact with various genes that are expressed in all or a subset of heart precursors to specify different heart cell fates. Based on this rationale, a novel gene, apontic (apt), which is expressed in the mesoderm and heart cells, has been cloned. apt encodes a protein that contains opa repeats between a hydrophobic domain and a stretch of asparagine (N). Phenotypic analysis reveals that apt mutants exhibit minor abnormalities in the heart of Drosophila. The heart beat rate is also greatly decreased in apt mutant embryos, suggesting that apt also plays a physiological role in Drosophila. Zinc finger homeodomain gene-1 (zfh-1) is expressed in the mesoderm and later in cardial as well as pericardial cells. This expression profile of zfh-1 has made it a potential candidate to be involved in some aspects of cardiac diversification. The EPCs are selectively missing in zfh-1 mutant embryos at late stages, suggesting that zfh-1 is essential for the proper development of EPCs. even-skipped (eve) itself has also been shown to be essential for even-skipped expressing pericardial cell (EPC) development. As in zfh-1 mutant embryos, removal of the function of eve causes the absence of the EPCs. This result suggests that both zfh-1 and eve act in the same genetic pathway to specify the EPC cell fate. An enhancer that is sufficient for mesodermal eve expression has been identified, and has been shown to be bound by zfh-1 protein in vitro. This result demonstrates that eve is a direct target of zfh-1 in the formation of EPCs. To examine the role of zfh-1 in the cardiogenesis of vertebrates I have identified a mouse zfh-1 homolog (mzfh-1) with a high degree of similarity in the organization of DNA binding domains and amino acids between Drosophila and mouse. The expression pattern of mzfh-1 resembles that of zfh-1. The missing EPCs can be restored in zfh-1 mutant embryos when mzfh-1 is over-expressed. This result demonstrates that zfh-1 and mzfh-1 are functionally interchangeable, and thus the function of zfh-1 is likely to be evolutionary conserved.Ph.D.Biological SciencesCellular biologyGeneticsMolecular biologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131549/2/9910002.pd
