Department of Biological Sciences, National University of Singapore, Singapore.
Adv Exp Med Biol. 2008;638:58-72. doi: 10.1007/978-0-387-09606-3_3.
The repeated appearance of somites is one of the most fascinating aspects of vertebrate embryogenesis. Recent studies identified complex regulatory circuits that provide the molecular basis for the "clock and wave front" model, postulated almost 30 years ago by Cooke and Zeeman. The highly coordinated process of somite formation involves several networks of molecular cascades including the Delta/Notch, Wnt, FGF and retinoid signalling pathways. Studies in mouse, Xenopus and especially chicken over the last decade have helped to understand the role and interactions of these pathways in somitogenesis. More recently, this has been supplemented by experiments in zebrafish. This animal model offers the possibility of performing large scale mutagenesis screens to identify novel factors and pathways involved in somitogenesis. Molecular cloning of zebrafish somite mutants mainly resulted in genes that belong to the Delta/Notch pathway and therefore underlined the importance of this pathway during somitogenesis. The fact that other pathways have not yet been identified by genetic screening in this species was assumed to be caused by functional redundancy of duplicated genes in zebrafish. In 2000, a large-scale mutagenesis screen has been initiated in Kyoto, Japan using the related teleost medaka (Oryzias latipes). In this screen, mutants with unique phenotypes have been identified, which have not been described in zebrafish or mouse. In this chapter, we will review the progress that has been made in understanding the molecular control of somite formation in zebrafish and will discuss recent efforts to screen for novel phenotypes using medaka somitogenesis mutants.
体节的重复出现是脊椎动物胚胎发生中最引人入胜的方面之一。最近的研究确定了复杂的调节回路,为“时钟和波前”模型提供了分子基础,该模型是近 30 年前由 Cooke 和 Zeeman 提出的。体节形成的高度协调过程涉及几个分子级联网络,包括 Delta/Notch、Wnt、FGF 和视黄酸信号通路。在过去十年中,对小鼠、非洲爪蟾,特别是鸡的研究有助于理解这些通路在体节发生中的作用和相互作用。最近,这一研究又得到了斑马鱼实验的补充。这种动物模型提供了进行大规模诱变筛选的可能性,以鉴定参与体节发生的新因子和途径。斑马鱼体节突变体的分子克隆主要导致属于 Delta/Notch 途径的基因,因此强调了该途径在体节发生中的重要性。在这个物种中,其他途径尚未通过遗传筛选确定,这被认为是由于斑马鱼中重复基因的功能冗余所致。2000 年,日本京都发起了一项大规模的诱变筛选,使用相关的硬骨鱼——青鳉(Oryzias latipes)。在这个筛选中,已经鉴定出具有独特表型的突变体,这些突变体在斑马鱼或小鼠中没有被描述过。在这一章中,我们将回顾在理解斑马鱼体节形成的分子控制方面所取得的进展,并讨论最近使用青鳉体节发生突变体筛选新表型的努力。