Mann Tabea, Bodmer Rolf, Pandur Petra
Institute for Biochemistry and Molecular Biology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Development. 2009 Jan;136(2):317-26. doi: 10.1242/dev.022533. Epub 2008 Dec 15.
In mouse, the LIM-homeodomain transcription factor Islet1 (Isl1) has been shown to demarcate a separate cardiac cell population that is essential for the formation of the right ventricle and the outflow tract of the heart. Whether Isl1 plays a crucial role in the early regulatory network of transcription factors that establishes a cardiac fate in mesodermal cells has not been fully resolved. We have analyzed the role of the Drosophila homolog of Isl1, tailup (tup), in cardiac specification and formation of the dorsal vessel. The early expression of Tup in the cardiac mesoderm suggests that Tup functions in cardiac specification. Indeed, tup mutants are characterized by a reduction of the essential early cardiac transcription factors Tin, Pnr and Dorsocross1-3 (Doc). Conversely, Tup expression depends on each of these cardiac factors, as well as on the early inductive signals Dpp and Wg. Genetic interactions show that tup cooperates with tin, pnr and Doc in heart cell specification. Germ layer-specific loss-of-function and rescue experiments reveal that Tup also functions in the ectoderm to regulate cardiogenesis and implicate the involvement of different LIM-domain-interacting proteins in the mesoderm and ectoderm. Gain-of-function analyses for tup and pnr suggest that a proper balance of these factors is also required for the specification of Eve-expressing pericardial cells. Since tup is required for proper cardiogenesis in an invertebrate organism, we believe it is appropriate to include tup/Isl1 in the core set of ancestral cardiac transcription factors that govern a cardiac fate.
在小鼠中，LIM同源结构域转录因子胰岛1（Isl1）已被证明可界定一个独立的心脏细胞群体，该群体对于右心室和心脏流出道的形成至关重要。Isl1是否在中胚层细胞中建立心脏命运的转录因子早期调控网络中发挥关键作用尚未完全明确。我们分析了果蝇中Isl1的同源物tailup（tup）在心脏特化和背血管形成中的作用。Tup在心脏中胚层的早期表达表明Tup在心脏特化中发挥作用。事实上，tup突变体的特征是必需的早期心脏转录因子Tin、Pnr和背侧交叉1 - 3（Doc）减少。相反，Tup的表达依赖于这些心脏因子中的每一个，以及早期诱导信号Dpp和Wg。遗传相互作用表明tup在心脏细胞特化中与tin、pnr和Doc协同作用。胚层特异性功能丧失和拯救实验表明，Tup在外胚层中也发挥作用以调节心脏发生，并暗示不同的LIM结构域相互作用蛋白在中胚层和外胚层中的参与。tup和pnr的功能获得分析表明，这些因子的适当平衡对于表达Eve的心包细胞的特化也是必需的。由于tup在无脊椎动物中是正常心脏发生所必需的，我们认为将tup/Isl1纳入控制心脏命运的祖先心脏转录因子核心组是合适的。
