Frasch Manfred
Division of Developmental Biology, Department of Biology, Friedrich-Alexander University of Erlangen-Nürnberg, Staudtstr. 5, Erlangen 91058, Germany; Tel.: +49-9131-8528061.
J Cardiovasc Dev Dis. 2016 Jun;3(2). doi: 10.3390/jcdd3020020. Epub 2016 May 27.
The development of the dorsal vessel in is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs into studies of cardiogenesis in vertebrates. Many of the major components that control cardiogenesis were discovered based on candidate gene approaches and their functions were defined by employing the outstanding genetic tools and molecular techniques available in this system. More recently, approaches have been taken that aim to interrogate the entire genome in order to identify novel components and describe genomic features that are pertinent to the regulation of heart development. Apart from classical forward genetic screens, the availability of the thoroughly annotated genome sequence made new genome-wide approaches possible, which include the generation of massive numbers of RNA interference (RNAi) reagents that were used in forward genetic screens, as well as studies of the transcriptomes and proteomes of the developing heart under normal and experimentally manipulated conditions. Moreover, genome-wide chromatin immunoprecipitation experiments have been performed with the aim to define the full set of genomic binding sites of the major cardiogenic transcription factors, their relevant target genes, and a more complete picture of the regulatory network that drives cardiogenesis. This review will give an overview on these genome-wide approaches to heart development and on computational analyses of the obtained information that ultimately aim to provide a description of this process at the systems level.
果蝇背血管的发育是最早在遗传和分子水平上详细定义调控心脏发生关键机制的系统之一。由于进化保守性,这些发现也为脊椎动物心脏发生的研究提供了重要的参考。许多控制心脏发生的主要成分是基于候选基因方法发现的,其功能是通过利用该系统中可用的出色遗传工具和分子技术来定义的。最近,人们采取了旨在对整个基因组进行研究的方法,以识别新的成分并描述与心脏发育调控相关的基因组特征。除了经典的正向遗传筛选外,果蝇全基因组序列的详细注释使得新的全基因组方法成为可能,其中包括在正向遗传筛选中使用的大量RNA干扰(RNAi)试剂的产生,以及在正常和实验操作条件下对发育中心脏的转录组和蛋白质组的研究。此外,还进行了全基因组染色质免疫沉淀实验,目的是确定主要心脏发生转录因子的全套基因组结合位点、它们的相关靶基因,以及驱动心脏发生的调控网络的更完整图景。本综述将概述这些用于研究果蝇心脏发育的全基因组方法,以及对所获信息的计算分析,最终目的是在系统水平上描述这一过程。