Vogler Georg, Bodmer Rolf
Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
J Cardiovasc Dev Dis. 2015 Mar 1;2(1):2-16. doi: 10.3390/jcdd2010002.
Many of the major discoveries in the fields of genetics and developmental biology have been made using the fruit fly, With regard to heart development, the conserved network of core cardiac transcription factors that underlies cardiogenesis has been studied in great detail in the fly, and the importance of several signaling pathways that regulate heart morphogenesis, such as Slit/Robo, was first shown in the fly model. Recent technological advances have led to a large increase in the genomic data available from patients with congenital heart disease (CHD). This has highlighted a number of candidate genes and gene networks that are potentially involved in CHD. To validate genes and genetic interactions among candidate CHD-causing alleles and to better understand heart formation in general are major tasks. The specific limitations of the various cardiac model systems currently employed (mammalian and fish models) provide a niche for the fly model, despite its evolutionary distance to vertebrates and humans. Here, we review recent advances made using the embryo that identify factors relevant for heart formation. These underline how this model organism still is invaluable for a better understanding of CHD.
遗传学和发育生物学领域的许多重大发现都是通过果蝇取得的。在心脏发育方面,果蝇中构成心脏发生基础的核心心脏转录因子保守网络已得到深入研究,并且一些调节心脏形态发生的信号通路(如Slit/Robo)的重要性最初也是在果蝇模型中得以展现。最近的技术进步使得先天性心脏病(CHD)患者可获得的基因组数据大幅增加。这凸显了许多可能与CHD相关的候选基因和基因网络。验证候选CHD致病等位基因之间的基因及遗传相互作用,并更全面地了解心脏形成,是主要任务。尽管果蝇与脊椎动物和人类在进化上距离较远,但目前所采用的各种心脏模型系统(哺乳动物和鱼类模型)存在的特定局限性为果蝇模型提供了用武之地。在此,我们回顾利用果蝇胚胎取得的最新进展,这些进展确定了与心脏形成相关的因素。这些进展突显了这种模式生物对于更好地理解CHD仍然具有的重要价值。