Department of Basic Science, University of Tokyo, Komaba, Tokyo, Japan.
PLoS Comput Biol. 2010 Apr 29;6(4):e1000760. doi: 10.1371/journal.pcbi.1000760.
Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts express a group of genes in a definite order, which leads to the diversity of cell types. We produced all possible regulatory networks of these genes and examined their expression dynamics numerically. From the analysis, we identified requisite regulations and predicted an unknown factor to reproduce known expression profiles caused by loss-of-function or overexpression of the genes in vivo, as well as in the wild type. Following this, we evaluated the stability of the actual Drosophila network for sequential expression. This network shows the highest robustness against parameter variations and gene expression fluctuations among the possible networks that reproduce the expression profiles. We propose a regulatory module composed of three types of regulations that is responsible for precise sequential expression. This study suggests that the Drosophila network for sequential expression has evolved to generate the robust temporal expression for neuronal specification.
精确的基因表达时间协调对于许多发育过程至关重要。发育生物学中的一个核心问题是如何稳健地控制这种协调的表达模式。在果蝇中枢神经系统的胚胎发育过程中，称为神经母细胞的神经干细胞以确定的顺序表达一组基因，从而导致细胞类型的多样性。我们生成了这些基因的所有可能的调控网络，并通过数值方法研究了它们的表达动力学。通过分析，我们确定了必需的调控，并预测了一个未知的因素，以重现体内或野生型基因功能丧失或过表达引起的已知表达谱。在此之后，我们评估了实际的果蝇网络用于顺序表达的稳定性。在可能的网络中，该网络在重现表达谱方面具有最高的稳健性，具有针对参数变化和基因表达波动的稳定性。我们提出了一个由三种调控类型组成的调控模块，该模块负责精确的顺序表达。这项研究表明，果蝇的顺序表达网络已经进化为产生神经元特化的稳健的时间表达。
