EMBL/CRG Research Unit in Systems Biology, CRG-Centre de Regulació Genòmica, and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
Dev Biol. 2013 May 1;377(1):305-17. doi: 10.1016/j.ydbio.2013.01.010. Epub 2013 Jan 18.
Developmental processes are robust, or canalised: dynamic patterns of gene expression across space and time are regulated reliably and precisely in the presence of genetic and environmental perturbations. It remains unclear whether canalisation relies on specific regulatory factors (such as heat-shock proteins), or whether it is based on more general redundancy and distributed robustness at the network level. The latter explanation implies that mutations in many regulatory factors should exhibit loss of canalisation. Here, we present a quantitative characterisation of segmentation gene expression patterns in mutants of the terminal gap gene tailless (tll) in Drosophila melanogaster. Our analysis provides new insights into the dynamic mechanisms underlying gap gene regulation, and reveals significantly increased variability of gene expression in the mutant compared to the wild-type background. We show that both position and timing of posterior segmentation gene expression domains vary strongly from embryo-to-embryo in tll mutants. This variability must be caused by a vulnerability in the regulatory system which is hidden or buffered in the wild-type, but becomes uncovered by the deletion of tll. Our analysis provides evidence that loss of canalisation in mutants could be more widespread than previously thought.
发育过程是稳健的，或者说是有固定模式的：在遗传和环境干扰的情况下，基因表达的动态模式在空间和时间上能够可靠且精确地调控。目前尚不清楚这种固定模式是依赖于特定的调控因子（如热休克蛋白），还是基于网络层面更普遍的冗余和分布式稳健性。后一种解释意味着许多调控因子的突变应该会导致固定模式的丧失。在这里，我们对果蝇中末端缺口基因 tll 的突变体的分段基因表达模式进行了定量描述。我们的分析为缺口基因调控的动态机制提供了新的见解，并揭示了突变体与野生型背景相比，基因表达的可变性显著增加。我们表明，tll 突变体中后部分段基因表达域的位置和时间从一个胚胎到另一个胚胎都有很大的变化。这种可变性一定是由于调控系统的脆弱性造成的，这种脆弱性在野生型中被隐藏或缓冲，但在 tll 缺失时就会暴露出来。我们的分析提供了证据表明，突变体中固定模式的丧失可能比以前认为的更为广泛。
