robustness under functional constraint the genetic network for temporal expression in drosophila neurogenesis功能约束下的鲁棒性的遗传网络果蝇神经发生的时间表达.pdfVIP

Robustness under Functional Constraint: The Genetic Network for Temporal Expression in Drosophila Neurogenesis 1 2 1,3 1,4 Akihiko Nakajima *, Takako Isshiki , Kunihiko Kaneko , Shuji Ishihara 1 Department of Basic Science, University of Tokyo, Komaba, Tokyo, Japan, 2 Center for Frontier Research, National Institute of Genetics, Mishima, Shizuoka, Japan, 3 ERATO Complex Systems Biology Project, Japan Science and Technology Agency, Komaba, Tokyo, Japan, 4 PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan Abstract 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 expres