Decoding the LIM development code

During development a vast number of distinct cell types arise from dividing progenitor cells. Concentration gradients of ligands that act via cell surface receptors signal transcriptional regulators that repress and activate particular genes. LIM homeodomain proteins are an important class of transcriptional regulators that direct cell fate. Although in C. elegans only a single LIM homeodomain protein is expressed in a particular cell type, in vertebrates combinations of LIM homeodomain proteins are expressed in cells that determine cell fates. We have investigated the molecular basis of the LIM domain "code" that determines cell fates such as wing formation in Drosophilia and motor neuron formation in chicks. The basic code is a homotetramer of 2 LIM homeodomain proteins bridged by the adaptor protein, nuclear LIM interactor (NLI). A more complex molecular language consisting of a hexamer complex involving NLI and 2 LIM homeodomain proteins, Lhx3 and Isl1 determines ventral motor neuron formation. The same molecular "words" adopt different meanings depending on the context of expression of other molecular "words."