Developmental gene regulatory networks in the zebrafish embryo

The genomic developmental program operates mainly through the regulated expression of genes encoding transcription factors and signaling pathways. Complex networks of regulatory genetic interactions control developmental cell specification and fates. Development in the zebrafish, Danio rerio, has been studied extensively and large amounts of experimental data, including information on spatial and temporal gene expression patterns, are available. A wide variety of maternal and zygotic regulatory factors and signaling pathways have been discovered in zebrafish, and these provide a useful starting point for reconstructing the gene regulatory networks (GRNs) underlying development. In this review, we describe in detail the genetic regulatory subcircuits responsible for dorsoanterior-ventroposterior patterning and endoderm formation. We describe a number of regulatory motifs, which appear to act as the functional building blocks of the GRNs. Different positive feedback loops drive the ventral and dorsal specification processes. Mutual exclusivity in dorsal-ventral polarity in zebrafish is governed by intra-cellular cross-inhibiting GRN motifs, including vent/dharma and tll1/chordin. The dorsal-ventral axis seems to be determined by competition between two maternally driven positive-feedback loops (one operating on Dharma, the other on Bmp). This is the first systematic approach aimed at developing an integrated model of the GRNs underlying zebrafish development. Comparison of GRNs' organizational motifs between different species will provide insights into developmental specification and its evolution. The online version of the zebrafish GRNs can be found at http://www.zebrafishGRNs.org.