Pannier is a Transcriptional Target and Partner of Tinman during Drosophila Cardiogenesis

Abstract

During Drosophila embryogenesis, the homeobox gene tinman is expressed in the dorsal mesoderm where it functions in the specification of precursor cells of the heart, visceral, and dorsal body wall muscles. The GATA factor gene pannier is similarly expressed in the dorsal-most part of the mesoderm where it is required for the formation of the cardial cell lineage. Despite these overlapping expression and functional properties, potential genetic and molecular interactions between the two genes remain largely unexplored. Here, we show that pannier is a direct transcriptional target of Tinman in the heart-forming region. The resulting coexpression of the two factors allows them to function combinatorially in the regulation of cardiac gene expression, and a physical interaction of the proteins has been demonstrated in cultured cells. We also define functional domains of Tinman and Pannier that are required for their synergistic activation of the D-mef2 differentiation gene in vivo. Together, these results provide important insights into the genetic mechanisms controlling heart formation in the Drosophila model system.

MEF2C is activated by multiple mechanisms in a subset of T-acute lymphoblastic leukemia cell lines

“…[29][30][31][32][33][34][35][36][37][38][39] Most genes were neither expressed in PEER nor in CCRF-CEM as analyzed by RT-PCR. However, five genes (CALR, CRIPTO, JMJD2A, MEF2C and PITX2) were expressed in both cell lines, while NR2F2 was expressed in PEER only, indicating their potential activation by NKX2-5.…”

“…In Drosophila mef2 is regulated by the NKX2-5 ortholog tinman together with the GATA ortholog pannier. 35,36 In vertebrates several GATA homologous are known, 49 among which GATA4 interacts with NKX2-5 and GATA3 is expressed specifically in T-cells. 50,51 Accordingly, in five T-ALL cell lines analyzed we were able to detect GATA3 protein by western blotting (Figure 2c).…”

The ATP-sensitive potassium (K ATP ) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman

“…In vertebrates, GATA-4 provides the binding efficiency to Nkx2.5 in cardiomyocytes; therefore, these two transcription factors can act cooperatively to activate cardiac genes (27)(28)(29)(30). Similarly, the Drosophila counterparts Pnr and Tin physically interact and synergistically control cardiac gene expression of genes such as Dmef2 (12). To further characterize the role of Pnr in dSUR activation, we expressed Pnr panmesodermally and compared the expression of dSUR to that of dHand, which marks all cardiac lineages (31).…”

“…Tin has previously been shown to bind to the specific DNA sequence TNAAGTG (10). Until now, only seven genes have been suggested to be direct downstream targets of Tin: cardiac Tin itself, zinc-finger GATA transcription factor Pannier (Pnr), MADS box transcription factor Dmef2, structural protein ␤3-tublin, helix-loop-helix transcription factor dHAND, and the membrane proteins Tincar and Toll in cardiac primordial cells (10)(11)(12)(13)(14)(15)(16). Another potential Tin target is dSUR, which has a heart-specific segmental expression pattern that is identical to the late cardiac-restricted expression of Tin (17) and is speculated to be an effector molecule for cardiac performance.…”

Downstream of Homeotic Genes: In the Heart of Hox function

“…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.…”