Controlling Cell Fate Specification System by Key Genes Determined from Network Structure

摘要

class="head no_bottom_margin" id="sec6title">IntroductionNetwork systems produce dynamics of molecular activity in organisms, and such dynamics are thought to be the origin of biological functions (, , ). A variety of cell types originate in the diversity of steady states of gene expression. We recently developed a new theoretical framework (linkage logic theory) (, , ), with which key nodes for controlling nonlinear dynamics are identified only from network structure without assuming quantitative details, such as functional forms, parameters, or initial states. According to this theory, the dynamics of a system is controllable to converge on any solution by controlling a subset of nodes called a feedback vertex set (FVS). Therefore, if the dynamics of a GRN has multiple steady states, we should be able to reproduce them and control the dynamics of the system by manipulating the activities of FVS molecules alone.In the present study, we applied the linkage logic theory to a GRN that specifies cell fates in embryos of the ascidian Ciona intestinalis (type A; also called Ciona robusta). The network structure for the specification of cell fate has been determined by a genome-wide gene knockdown assay for regulatory genes that are expressed during embryogenesis () and was recently updated using data that had been accumulated after the initial construction (). Hence, if the fate decision is based on the steady states of this network, cell-type-specific gene expression patterns should be reproduced by manipulating the activities of FVS in the network. Here, we show that the minimum FVSs of this network contain only five factors and that the dynamics of the GRN is indeed controllable by these five FVS factors.