The homeodomain family of transcription factors plays a fundamental role in a diverse set of functions that include body plan specification, pattern formation, and cell fate determination during metazoan development. Members of this family are characterized by a helix-turn-helix DNA-binding motif known as the homeodomain. Homeodomain proteins regulate various cellular processes by specifically binding to the transcriptional control region of a target gene. These proteins have been conserved across a diverse range of species, from yeast to human.? ? Work over the past year has focused on the Hox genes, which are critical to many morphological innovations of bilaterian animals. However, early Hox evolution remains obscure. Phylogenetic and genomic analysis on the cnidarian sea anemone Nematostella vectensis has yielded results that challenge recent claims that the Hox code is a bliaterian invention and that no """"""""true"""""""" Hox genes exist in the phylum Cnidaria. Phylogenetic analyses of 18 Hox-related genes from Nematostella identify putative Hox1, Hox2, and Hox9+ genes. Statistical comparisons among competing hypotheses bolster these findings, including an explicit consideration of the gene losses implied by alternate topologies. When considered alongside in situ hybridization experiments aimed at determining the expression of these genes (conducted by our colleagues at Boston University), it becomes apparent that these Hox genes have some role in """"""""dorsoventral"""""""" patterning.? ? Based on this work, it appears that a cluster of anterior and posterior Hox genes, as well as a ParaHox cluster of genes, evolved prior to the cnidarian-bilaterian split. There is evidence to suggest that these clusters were formed from a series of tandem gene duplication events and played a role in patterning both the primary and secondary body axes in a bilaterally symmetrical common ancestor. Several basal Hox-related genes exhibit expression patterns that suggest their involvement in neurogenesis and the origin of these may have coincided with the genesis of the metazoan nervous system. Cnidarians and bilaterians shared a common ancestor some 570 to 700 million years and as such derived from a common body plan; our work reveals several conserved genetic components within these two diverse lineages, and is consistent with the hypothesis that a set of developmental rules set up in the common ancestor of Cnidarians and Bilaterians are still at work today.? ? Finally, the workgroup continues to oversee the curation and maintenance of the Homeodomain resource, a searchable collection of information for the homeodomain protein family. The resource is organized in a compact form and provides user-friendly interfaces for both querying the component databases and assembling customized datasets. The current release contains 4,385 full-length homeodomain-containing sequences covering 546 distinct organisms, 50 experimentally-derived structures, 90 homeodomain interactions, 91 homeodomain DNA-binding sites, 181 homeodomain proteins implicated in human genetic disorders, and 38 homeodomain proteins with documented allelic variants. The information available on both allelic variants and experimentally-derived protein-protein interactions has been significantly expanded, encompassing information from new sources, such as the Human Gene Mutation Database and the Biomolecular Interaction Network (BIND). All experimentally-derived protein-protein interaction data derived from the literature has been contributed to BIND as well. The Homeodomain Resource is freely available through the World Wide Web at http://research.nhgri.nih.gov/homeodomain/.
