Three new Hox gene regulators in Caenorhabditis elegans

Abstract

Hox genes are expressed in distinct domains and control positional identity along the anterior-posterior axis during animal development. Despite many years of research, how the expression domains of Hox genes are established and maintained and how the specificity of Hox proteins is achieved is not well understood. In order to identify more Hox gene regulators, our laboratory has used C. elegans male ray development as a model system. From a mutant screen, I isolated and characterized three new genes that regulate the expression and function of Hox genes: sop-1, sop-2 and sop-3.;The Hox genes mab-5 and egl-5 are required for the epidermal cell V6 to generate five sensory organs, called rays. pal-1 (the homolog of Drosophila transcription factor caudal) acts cell autonomously to activate mab-5 expression in V6. Therefore, in pal-1 mutants the V6 rays are missing due to the failure of activation of mab-5. Mutations in sop-1, sop-2, and sop-3 suppress the V6 ray missing phenotype caused by pal-1 mutation. sop-1 encodes the homolog of human TRAP230, a component of the Mediator complex, required ubiquitously in eukaryotes for transducing signals from transcriptional activators or repressors to RNA polymerase Il. sop-3 encodes a novel protein with characteristics of a transcriptional factor, which might also be a component of the Mediator complex. Like the function of the Mediator complex in yeast, sop-1 and sop-3 confer regulatory stringency on the expression of pal-1 and egl-5. To do so, sop-1 and sop-3 prevent the Wnt signaling pathway from activating pal-1 and egl-5. sop-3 also modulates the function of MAB-5 and Wnt signaling to ensure the expression of egl-5 in the appropriate branch of the V6 lineage.;In contrast to sop-1 and sop-3, whose effects seem to be restricted to V6, sop-2 is involved in maintaining the global expression pattern of Hox genes. In sop-2 mutants, all four Hox genes in the C. elegans Hox cluster are ectopically expressed, resulting in massive homeotic transformations. sop-2 may define a new pathway involved in preventing the expression of Hox genes beyond their normal boundaries.