Institute of Biology of the Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
Dev Cell. 2013 Jan 14;24(1):64-75. doi: 10.1016/j.devcel.2012.12.001.
Biological systems may perform reproducibly to generate invariant outcomes, despite external or internal noise. One example is the C. elegans vulva, in which the final cell fate pattern is remarkably robust. Although this system has been extensively studied and the molecular network underlying cell fate specification is well understood, very little is known in quantitative terms. Here, through pathway dosage modulation and single molecule fluorescence in situ hybridization, we show that the system can tolerate a 4-fold variation in genetic dose of the upstream signaling molecule LIN-3/epidermal growth factor (EGF) without phenotypic change in cell fate pattern. Furthermore, through tissue-specific dosage perturbations of the EGF and Notch pathways, we determine the first-appearing patterning errors. Finally, by combining different doses of both pathways, we explore how quantitative pathway interactions influence system behavior. Our results highlight the feasibility and significance of launching experimental studies of robustness and quantitative network analysis in genetically tractable, multicellular eukaryotes.
生物系统可以在存在外部或内部噪声的情况下重复执行以产生不变的结果。一个例子是秀丽隐杆线虫的阴道，其最终的细胞命运模式非常稳健。尽管该系统已被广泛研究，并且细胞命运指定的分子网络已被很好地理解，但在定量方面知之甚少。在这里，通过途径剂量调节和单分子荧光原位杂交，我们表明该系统可以在不改变细胞命运模式的情况下耐受上游信号分子 LIN-3/表皮生长因子 (EGF) 的遗传剂量变化 4 倍。此外，通过对 EGF 和 Notch 途径进行组织特异性剂量扰动，我们确定了最早出现的模式错误。最后，通过组合两种途径的不同剂量，我们探讨了定量途径相互作用如何影响系统行为。我们的研究结果强调了在遗传上易于处理的多细胞真核生物中开展稳健性和定量网络分析实验研究的可行性和重要性。
