  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 sequentially express a group of genes in a definite order, which
generates the diversity of cell types. By producing all possible regulatory
networks of these genes and examining their expression dynamics numerically, we
identify requisite regulations and predict 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. We then evaluate 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 kinds of regulations
which is responsible for precise sequential expression. The present study
suggests an underlying principle on how biological systems are robustly
designed under functional constraint.
