Irx7 gene regulatory network for zebrafish retinal development.

<p>A gene regulatory network was constructed using the expression patterns of <i>irx7</i> downstream targets as characterized in this study. The specification circuit of the network consists of TFs that specify different retinal cell types while the differentiation circuit consists of genes that carry out cell type specific functions. For example, <i>opsins</i> in the photoreceptors are responsible for visual signal transduction. Genes that have not been fully characterized yet are represented by a generic gene (<i>cell type</i>-<i>genes</i>) in the differentiation circuit. The activation of these “<i>cell type</i>-genes” by <i>irx7</i>, as well as by other TFs, symbolizes the differentiation of the corresponding cell types driven by the specification circuit. For GCs, an additional <i>“GC genes for dendritic outgrowth”</i> is created to distinguish the specific effects of <i>irx7</i> knockdown on their dendritic outgrowth (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036145#pone-0036145-g005" target="_blank">Figure 5</a>). If the actual location of the interaction is not well defined, the domain/cell type in which the effector gene is expressed will be used. In addition, different retinal regions, including, GCL, INL and ONL can have cellular interaction (≪-≫) that can trigger signal transduction and in turn modulate gene expression. Note that the network topology is a static global view which consists of information obtained from different stages and studies, thus some genes may have both positive and negative inputs if the regulation is dynamical during development. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036145#pone.0036145.s004" target="_blank">File S2</a> for supporting evidence of the connections and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036145#pone.0036145.s002" target="_blank">Figure S2</a> for a comprehensive network with additional connections between these genes as extracted from other literature references.