HDA-1

From another genetic screen, we found another mutation that affects cell migration. We cloned the gene and determined that it corresponds to the previously described hda-1, which encodes a histone deacetylase. Histone deacetylases often function as general negative regulators of gene expression by removing specific chemical tags from histones, proteins involved in packaging DNA within the nucleus. Histone deacetylases also have been shown to affect other proteins, including tubulin. We were the first to report that mutations in hda-1 produce widespread cell migration defects, particularly within the nervous system. For example, see the HSN axon pathfinding defects in hda-1 mutants shown in the Figure. Furthermore, we find that HDA-1 protein accumulates within the axons and dendrites of the nervous system, raising the possibility that HDA-1 might modify important target proteins in those neuronal extensions. We currently have two models for HDA-1 function. HDA-1 may regulate gene expression patterns in neurons through modification of histones, or it may modify and regulate proteins involved in cell migration.

Top panel shows HSN axons in wild type. The lower three panels show HSN axon defects in hda-1(cw2) mutants, where axons branch and extend in inappropriate direction (middle panel) or wander along the lateral body wall (two bottom panels).