A Regulatory Network Controlling Drosophila Development

Abstract

We have used a combination of genetics, microarray assays, bioinformatics methods and experimental perturbation to determine the genomic regulatory program underlying the early development of the fruitfly, Drosophila melanogaster. The process of gastrulation is initiated by a sequence-specific transcription factor called Dorsal. The Dorsal protein is distributed in a broad concentration gradient across the dorsal-ventral axis of the early embryo, with peak levels in ventral regions and progressively lower levels in more dorsal regions. The Dorsal gradient controls gastrulation by regulating a variety of target genes in a concentration-dependent fashion. Microarray assays have identified at least 50 genes that display localized expression across the dorsal-ventral axis and something like 30 of these genes are directly regulated by the Dorsal gradient. That is, these genes contain nearby enhancers with essential Dorsal binding sites. Most of the enhancers have been identified and experimentally validated. Computational analysis suggests that the threshold readout of the Dorsal gradient depends on the quality of the best Dorsal binding sites contained in the enhancer. Enhancers with Dorsal binding sites containing a poor match to the consensus sequence are activated by high levels of the gradient, while trhose enhancers with good matches to the consensus are regulated by intermediate or low levels of the gradient.