Gnathostomes have two lineages of Otx genes, Otx1 and Otx2, as cognate
s of a Drosophila head gap gene, orthodenticle. Previous studies with
mutant mice have demonstrated that they play essential roles in the de
velopment of rostral head. To shed lights on the evolution of the rost
ral head in vertebrates we isolated their cognates in the Japanese mar
ine lamprey, Lampetra japonica. The lamprey genome appeared to have tw
o Otx cognantes, LjOtxA and LjOtxB. Phylogenetic analyses suggest that
LjOtxA clusters with gnathostome Otx2 genes, but LjOtxB does not belo
ng to either the Otx1 or Otx2 lineage. LjOtxA was expressed in the for
ebrain and midbrain with the caudal limit possibly at the midbrain/hin
dbrain junction as gnathostome Otx cognates are, but LjOtxB was not ex
pressed in the brain. No Otx1 or Otx2 cognates are known in gnathostom
es that are not expressed in the brain. Both LjOtxA and LjOtxB were ex
pressed in the olfactory placode, epiphysis, optic stalks, and lower a
nd upper lips. LjOtxB was also expressed in the eyes, where no LjOtxA
transcripts were detected, Thus, Otx1 and Otx2 functions for the devel
opment of forebrain and midbrain in gnathostomes appear to be shoulder
ed by LjOtxA alone in the lamprey. LjOtxB may have diverged from the s
tem of the Otx1 and Otx2 lineages and evolved independently.