The Dorsocross T-box genes are key components of the regulatory network controlling early cardiogenesis inDrosophila

Abstract

factor. Our loss-and gain-of-function studies, as well as the observed genetic interactions among Dorsocross, tinman and pannier, suggest that co-expression of these three genes in the cardiac mesoderm, which also involves crossregulation, plays a major role in the specification of cardiac progenitors. After cardioblast specification, the Dorsocross genes are re-expressed in a segmental subset of cardioblasts, which in the heart region develop into inflow valves (ostia). The integration of this new information with previous findings has allowed us to draw a more complete pathway of regulatory events during cardiac induction and differentiation in Drosophila. 4912 Bodmer, 2003), at a time when the segmentally distributed cardiac progenitors coalesce into a continuous band of cells. However, one important and direct consequence of Wg signals is the induction of sloppy paired (slp1 and slp2) in striped domains in the early mesoderm (Riechmann et al., 1997;Lee and Frasch, 2000). The slp genes encode forkhead domain repressor factors, which prevent the induction of visceral mesoderm regulators by Dpp that would otherwise interfere with cardiac induction in the presumptive cardiogenic areas (Zaffran et al., 2001). Research article DevelopmentIn addition to excluding these inappropriate regulators from the cardiogenic areas, wg is thought to promote the formation of both pericardial and myocardial progenitors also in a direct fashion. Indeed, such a mechanism operates during the specification of one specific subset of pericardial cells, termed Eve-PCs, and the induction of the even-skipped (eve) gene in progenitors of these cells requires binding sites for the Wg effector Pangolin (Pan, also known as dTCF) in combination with binding sites for Tinman and the Dpp-effectors Mad and Medea (Halfon et al., 2000;Knirr and Frasch, 2001;Han et al., 2002). Hence, the combinatorial inputs from Wg, Dpp and the cardiogenic competence factor Tinman are directly integrated at the level of the enhancer of a pericardial regulatory gene. Based upon the available genetic data on cardioblast specification, it is likely that an analogous integration of Wg and Dpp signals also occurs during the induction of certain early-acting myocardial regulatory genes. However, clear candidates for common targets of Wg and Dpp in myocardial development have not been described.Our current study identifies the Dorsocross T-box genes as crucial new components that mediate the combinatorial activities of Wg and Dpp during early steps of myocardial induction. The Dorsocross (Doc) locus encodes a cluster of three genes, Doc1, Doc2 and Doc3, that are closely related in terms of their T-box sequences and embryonic expression patterns (Reim et al., 2003). Our previous work has identified important roles of these genes during amnioserosa development and epidermal patterning of the embryo (Reim et al., 2003). We now show that, within the mesoderm, the Doc genes have an essential role for the formation of cardioblasts and a subset of pericardial cells. The indu...

Specification of theC. elegansMS blastomere by the T-box factor TBX-35

“…Tbx regulators are essential for heart development in vertebrates; in humans, mutations in Tbx genes lead to congenital cardiac defects (Plageman and Yutzey, 2005). Recently, Tbx genes have been found to be important for development of heart in Drosophila, in which the Tbx genes Dorsocross, midline and H15 function in the specification and formation of cardiac cells (Miskolczi-McCallum et al, 2005;Reim and Frasch, 2005). Although C. elegans lacks a circulatory system, its pharynx has some similarities to a heart, as it is a pumping organ containing contractile muscle that is distinct from body muscle (Avery and Shtonda, 2003;Okkema et al, 1993).…”

The Dorsocross T-box transcription factors promote tissue morphogenesis in the Drosophila wing imaginal disc

“…Dorsocross (Doc), the Drosophila Tbx6 subfamily gene cluster, encodes three closely related proteins: Doc1, Doc2 and Doc3, which are essential for proper development of amnioserosa, heart and hindgut (Lo and Frasch, 2001;Reim et al, 2003;Hamaguchi et al, 2004;Reim and Frasch, 2005). The three genes are arranged in a cluster and are expressed in identical patterns in the embryo.…”

Downstream of Homeotic Genes: In the Heart of Hox function

“…1A and B and D-D"). [32][33][34] At stage 13, cardiac cells undergo a mesenchyme/ epithelium transition 35 to form two continuous rows of cells, one on each side of the embryo. These two rows of epithelial cells, associated with the PCs, migrate towards the dorsal midline during dorsal closure (stage 14/15).…”

“…A number of factors that are required for the specification and the differentiation of the different cardiac cell subtypes could be candidate cofactors to modulate Hox activity. 33,38,39,41,42,[74][75][76][77][78][79][80][81][82] (6) At metamorphosis, the activation of the ecdysone-induced signaling pathway produces some changes in the Tin-CMs which are in turn responsible for the switch of abdA activity: AbdA switches from an activator to a repressor, at least regarding Ih and Ndae1 transcription. Knowing the signal, the ecdysone, responsible for the Hox activity modification should facilitate the search of candidate factors involved in this ecdysone-dependent change of abdA activity.…”