Open AccessDynamics of Regulatory Networks in the Developing Mouse Retina
Author(s) -
Woochang Hwang,
László Hackler,
George Y. Wu,
Hongkai Ji,
Donald J. Zack,
Jiang Qian
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0046521
Subject(s) - gene regulatory network , biology , computational biology , network motif , network analysis , microrna , regulation of gene expression , transcription factor , network dynamics , gene , eye development , retinal , biological network , genetics , gene expression , biochemistry , physics , mathematics , discrete mathematics , quantum mechanics
Understanding gene regulation is crucial to dissect the molecular basis of human development and disease. Previous studies on transcription regulatory networks often focused on their static properties. Here we used retinal development as a model system to investigate the dynamics of regulatory networks that are comprised of transcription factors, microRNAs and other protein-coding genes. We found that the active sub-networks are topologically different at early and late stages of retinal development. At early stages, the active sub-networks tend to be highly connected, while at late stages, the active sub-networks are more organized in modular structures. Interestingly, network motif usage at early and late stages is also distinct. For example, network motifs containing reciprocal feedback regulatory relationships between two regulators are overrepresented in early developmental stages. Additionally, our analysis of regulatory network dynamics revealed a natural turning point at which the regulatory network undergoes drastic topological changes. Taken together, this work demonstrates that adding a dynamic dimension to network analysis can provide new insights into retinal development, and we suggest the same approach would likely be useful for the analysis of other developing tissues.