Function and evolution of Otx proteins

Otx proteins comprise an important class of homeodomain-containing transcription factors known for their essential roles in anterior head formation. Here, we briefly review the basic structural features and functional diversity of Otx proteins and describe current views on the evolution of Otx genes in metazoans. A prominent feature of Otx homeodomains is a lysine residue at position 9 of the recognition helix, which confers high-affinity binding to TAATCC/T elements on DNA. Besides their DNA binding properties, surprisingly little is known about how Otx proteins function to activate target genes in selective regions of the embryo. While an essential and ancient role for Otx is to pattern the anterior regions of the head, drawing conclusions about primordial functions is difficult. This is because Otx proteins have been recruited for numerous developmental roles, and derived functions have often evolved to meet the specialized requirements of individual taxonomic groups. In sea urchin embryos, one form of Otx may have been co-opted by the Wnt-β-catenin signaling pathway. The consequence of such an evolutionary event would be to link a highly conserved signal transduction pathway to a set of novel downstream genes that make use of Otx for their transcription.