Rida Padmashree C G, Le Minh Nguyet, Jiang Yun Jin
Laboratory of Developmental Signalling and Patterning, Institute of Molecular and Cell Biology, National University of Singapore, Singapore 117604, Singapore.
Dev Biol. 2004 Jan 1;265(1):2-22. doi: 10.1016/j.ydbio.2003.07.003.
Vertebrate segmentation is manifested during embryonic development as serially repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle and dermis. Many theoretical models including the "clock and wavefront" model have been proposed. There is compelling genetic evidence showing that Notch-Delta signaling is indispensable for somitogenesis. Notch receptor and its target genes, Hairy/E(spl) homologues, are known to be crucial for the ticking of the segmentation clock. Through the work done in mouse, chick, Xenopus and zebrafish, an oscillator operated by cyclical transcriptional activation and delayed negative feedback regulation is emerging as the fundamental mechanism underlying the segmentation clock. Ubiquitin-dependent protein degradation and probably other posttranslational regulations are also required. Fgf8 and Wnt3a gradients are important in positioning somite boundaries and, probably, in coordinating tail growth and segmentation. The circadian clock is another biochemical oscillator, which, similar to the segmentation clock, is operated with a negative transcription-regulated feedback mechanism. While the circadian clock uses a more complicated network of pathways to achieve homeostasis, it appears that the segmentation clock exploits the Notch pathway to achieve both signal generation and synchronization. We also discuss mathematical modeling and future directions in the end.
脊椎动物的体节形成在胚胎发育过程中表现为一系列重复的单位，即体节，体节会发育成椎骨、肋骨、骨骼肌和真皮。包括“时钟和波阵面”模型在内，已经提出了许多理论模型。有令人信服的遗传学证据表明，Notch-Delta信号通路对于体节发生是不可或缺的。已知Notch受体及其靶基因Hairy/E(spl)同源物对于体节时钟的运转至关重要。通过在小鼠、鸡、非洲爪蟾和斑马鱼上开展的研究工作，一种由周期性转录激活和延迟负反馈调节驱动的振荡器正逐渐成为体节时钟的基本机制。泛素依赖性蛋白质降解以及可能的其他翻译后调控也必不可少。Fgf8和Wnt3a梯度对于确定体节边界很重要，并且可能对于协调尾部生长和体节形成也很重要。昼夜节律时钟是另一种生化振荡器，与体节时钟类似，它通过负转录调节反馈机制运行。虽然昼夜节律时钟利用更复杂的信号通路网络来实现体内平衡，但体节时钟似乎利用Notch信号通路来实现信号产生和同步。最后我们还讨论了数学建模和未来方向。
