Jagla K, Frasch M, Jagla T, Dretzen G, Bellard F, Bellard M
Institut de Génétique et de Biologie Moléculaire et Cellulaire CNRS/INSERM/ULP, Collège de France, CU de Strasbourg.
Development. 1997 Sep;124(18):3471-9. doi: 10.1242/dev.124.18.3471.
The embryonic heart precursors of Drosophila are arranged in a repeated pattern of segmental units. There is growing evidence that the development of individual elements of this pattern depends on both mesoderm intrinsic patterning information and inductive signals from the ectoderm. In this study, we demonstrate that two homeobox genes, ladybird early and ladybird late, are involved in the cardiogenic pathway in Drosophila. Their expression is specific to a subset of cardioblast and pericardial cell precursors and is critically dependent on mesodermal tinman function, epidermal Wingless signaling and the coordinate action of neurogenic genes. Negative regulation by hedgehog is required to restrict ladybird expression to two out of six cardioblasts in each hemisegment. Overexpression of ladybird causes a hyperplasia of heart precursors and alters the identity of even-skipped-positive pericardial cells. Loss of ladybird function leads to the opposite transformation, suggesting that ladybird participates in the determination of heart lineages and is required to specify the identities of subpopulations of heart cells. We find that both early Wingless signaling and ladybird-dependent late Wingless signaling are required for proper heart formation. Thus, we propose that ladybird plays a dual role in cardiogenesis: (i) during the early phase, it is involved in specification of a segmental subset of heart precursors as a component of the cardiogenic tinman-cascade and (ii) during the late phase, it is needed for maintaining wingless activity and thereby sustaining the heart pattern process. These events result in a diversification of heart cell identities within each segment.
果蝇的胚胎心脏前体以节段单元的重复模式排列。越来越多的证据表明，这种模式中各个元素的发育既依赖于中胚层内在的模式形成信息，也依赖于外胚层的诱导信号。在本研究中，我们证明了两个同源异型盒基因，即早期瓢虫基因和晚期瓢虫基因，参与了果蝇的心脏发生途径。它们的表达特定于成 cardioblast 和心包细胞前体的一个子集，并且严重依赖于中胚层的 tinman 功能、表皮的无翅信号以及神经源性基因的协同作用。刺猬信号的负调控是将瓢虫基因的表达限制在每个半节段的六个成 cardioblast 中的两个所必需的。瓢虫基因的过表达导致心脏前体的增生，并改变了偶数跳变阳性心包细胞的身份。瓢虫基因功能的丧失导致相反的转变，这表明瓢虫基因参与了心脏谱系的确定，并且是确定心脏细胞亚群身份所必需的。我们发现，早期无翅信号和依赖瓢虫基因的晚期无翅信号对于正常的心脏形成都是必需的。因此，我们提出瓢虫基因在心脏发生中起双重作用：（i）在早期阶段，它作为心脏发生的 tinman 级联反应的一个组成部分，参与心脏前体节段子集的特化；（ii）在晚期阶段，它是维持无翅活性从而维持心脏模式过程所必需的。这些事件导致每个节段内心脏细胞身份的多样化。
