Charakterisierung der Rolle des Transkriptionsfaktors tailup in der Herzentwicklung von Drosophila melanogaster

Abstract

The heart of Drosophila melanogaster is a simple tube that consists of contractile myocardial cells, which are surrounded by pericardial cells. All heart cells are characterized by the expression of specific combinations of transcription factors. The ectodermal growth factors Decapentaplegic (Dpp) (TGFß family) and Wingless (Wg) (Wnt family) induce together with the mesodermal Nk-2 factor Tinman (Tin) bilaterally cardiac mesoderm. Additional transcription factors that are required for the proper specification of cardiac cells are the Tbx factor Dorsocross (Doc) and the GATA factor Pannier (Pnr). This study focused on the functional analysis of the LIM-homeodomain transcription factor Tailup (Tup), which is homolog to vertebrate Islet-1 (Isl-1) during Drosophila heart development. Analyses of the expression pattern showed that Tup is expressed early in the cardiac mesoderm. During development Tup expression is detected in all myocardial and in the majority of pericardial cells of the linear heart tube. The functional analyses showed that Tup is also required for the correct specification of heart cells since tup mutants are characterized by reduced expression of Tin, Doc, Pnr. Conversely, the correct expression of Tup depends on tin, Doc and pnr, as well as on wg and dpp. Additionally, it was demonstrated that tup interacts genetically with tin, Doc and pnr during heart development. Next, germband and cell specific loss- and gain-of-function studies of tup were performed. Germband specific inhibition of tup using a deletion construct demonstrated the requirement of Tup during heart development in the mesoderm and the ectoderm. Additionally, it was shown that not only the homeodomain but also the LIM-domains are necessary for the function of Tup. Ectodermal inhibition of Tup function led to a heart phenotype which could be explained partially by reduced expression of dpp. Mesodermal overexpression of Tup alone could only weakly induce ectopic heart cells or expand cardiac marker gene expression. Overexpression of tup and pnr suggest that specification of Eve positive cells need a proper balance of Tup and Pnr activity. Overexpression or inhibition of Tup in the pericardial cell lineage has positive or negative effects on the amount of Odd pericardial cells.