Molecular mechanisms of cell fate specification in Drosophila limb development

In animal development, cell fate specification is controlled by positional inputs at the local and regional levels. Integration of this information occurs at the level of DNA, in the sequences of the cis -regulatory elements controlling target gene expression. During development of the Drosophila limb, the Distalless ( DII) selector gene is initially controlled by the axial coordinate system present in the embryo. The fates of these cells are subsequently subdivided into discrete lineages by the signals that pattern the appendage. We have determined that a succession of cis-regulatory elements is used to integrate this information over developmental time, directly incorporating transient and antagonistic signaling inputs with autoregulatory inputs to generate stable transcriptional output. These studies have revealed the molecular logic of developmental gene expression programs and their ability to maximize the versatility of a minimal set of signals to generate complex and morphologically diverse organisms. Lastly, we have initiated studies examining the chromatin organization of the DII locus in the dynamic nuclear environment.