Otx proteins comprise an important class of homeodomain-containing transcri
ption factors known for their essential roles in anterior head formation. H
ere, we briefly review the basic structural features and functional diversi
ty 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, surpris
ingly little is known about how Otx proteins function to activate target ge
nes in selective regions of the embryo. While an essential and ancient role
for Otx is to pattern the anterior regions of the head, drawing conclusion
s about primordial functions is difficult. This is because Otx proteins hav
e been recruited for numerous developmental roles, and derived functions ha
ve often evolved to meet the specialized requirements of individual taxonom
ic groups. In sea urchin embryos, one form of Otx may have been co-opted by
the Wnt-beta-catenin signaling pathway. The consequence of such an evoluti
onary 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 transcri
ption, (C) 1999 Academic Press.