Su M T, Venkatesh T V, Wu X, Golden K, Bodmer R
Department of Biology, University of Michigan, Ann Arbor 48109-1048, USA.
Mech Dev. 1999 Feb;80(2):125-32. doi: 10.1016/s0925-4773(98)00197-x.
In an effort to isolate genes required for heart development and to further our understanding of cardiac specification at the molecular level, we screened PlacZ enhancer trap lines for expression in the Drosophila heart. One of the lines generated in this screen, designated B2-2-15, was particularly interesting because of its early pattern of expression in cardiac precursor cells, which is dependent on the homeobox gene tinman, a key determinant of heart development in Drosophila. We isolated and characterized a gene in the vicinity of B2-2-15 that exhibits an identical expression pattern than the reporter gene of the enhancer trap. The product of his gene, apontic (apt; see also "Gellon et al., 1997"), does not appear to have any homology with known genes. apt mutant embryos show distinct abnormalities in heart morphology as early as mid-embryonic stages when the heart tube assembles, in that segments of heart cells (those of myocardial and pericardial identity) are often missing. Most strikingly, however, apt mutant embryos or larvae only develop a much reduced heart rate, perhaps because of defects in the assembly of an intact heart tube and/or because of defects in the function or physiological control of the myocardial cells, which normally mediate heart contractions. These cardiac defects may be the cause of death of these mutants during late embryonic or early larval stages.
为了分离心脏发育所需的基因，并在分子水平上进一步加深我们对心脏特化的理解，我们筛选了PlacZ增强子捕获系，以寻找在果蝇心脏中表达的系。在这个筛选中产生的一个系，命名为B2-2-15，特别有趣，因为它在心脏前体细胞中的早期表达模式，这种模式依赖于同源异型框基因tinman，tinman是果蝇心脏发育的关键决定因素。我们在B2-2-15附近分离并鉴定了一个基因，该基因表现出与增强子捕获的报告基因相同的表达模式。这个基因的产物apontic（apt；另见“Gellon等人，1997年”）似乎与已知基因没有任何同源性。apt突变胚胎早在胚胎中期心脏管组装时就显示出心脏形态的明显异常，即心脏细胞的部分（那些具有心肌和心包特征的细胞）经常缺失。然而，最引人注目的是，apt突变胚胎或幼虫的心率大大降低，这可能是因为完整心脏管组装存在缺陷和/或因为心肌细胞的功能或生理控制存在缺陷，而心肌细胞通常介导心脏收缩。这些心脏缺陷可能是这些突变体在胚胎后期或幼虫早期死亡的原因。
