Otx1 gene-controlled morphogenesis of the horizontal semicircular canal and the origin of the gnathostome characteristics

The horizontal semicircular canal of the inner ear is a unique feature of g nathostomes and is predated by the two vertical semicircular canals, which are already present in lampreys and some fossil, armored jawless vertebrate s regarded as close relatives of gnathostomes. Inactivation in mice of the orthodenticle-related gene Otx1 results in the absence of this structure. I n bony fishes and tetrapods (osteichthyans), this gene belongs to a small m ultigene family comprising at least two orthology classes, Otx1 and Otx2. W e report that, as in the mouse, xenopus and zebrafish, Otx1- and Otx2-relat ed genes are present in a chondrichthyan, the dogfish Scyliorhinus canicula , with an Otx1 expression domain in the otocyst very similar to those obser ved in osteichthyans. A strong correlation is thus observed in extant verte brates between the distribution of the horizontal semicircular canal and th e presence of an Otx1 ortholog expressed in the inner ear, which supports t he hypothesis that the absence of this characteristic in Otx1(-/-) mice may correspond to an atavism. The same conclusion applies to two other gnathos tome-specific characteristics also deleted in Otx1(-/-) mice, the utriculos accular duct and the ciliary process. Together with functional analyses of Otx1 and Otx2 genes in mice and comparative analyses of the Otx gene famili es characterized in chordates, these discoveries lead to the hypothesis tha t some of the anatomic characteristics of gnathostomes have appeared quite suddenly and almost simultaneously in vertebrate evolution, possibly as a c onsequence of gene functional diversifications following duplications of an ancestral chordate gene.