Evol Dev 2000 Jan 01;24:186-93. doi: 10.1046/j.1525-142x.2000.00062.x.

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

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The horizontal semicircular canal of the inner ear is a unique feature of gnathostomes and is predated by the two vertical semicircular canals, which are already present in lampreys and some fossil, armored jawless vertebrates regarded as close relatives of gnathostomes. Inactivation in mice of the orthodenticle-related gene Otx1 results in the absence of this structure. In bony fishes and tetrapods (osteichthyans), this gene belongs to a small multigene family comprising at least two orthology classes, Otx1 and Otx2. We report that, as in the mouse, xenopus and zebrafish, Otx1- and Otx2-related genes are present in a chondrichthyan, the dogfish Scyliorhinus canicula, with an Otx1 expression domain in the otocyst very similar to those observed in osteichthyans. A strong correlation is thus observed in extant vertebrates between the distribution of the horizontal semicircular canal and the presence of an Otx1 ortholog expressed in the inner ear, which supports the hypothesis that the absence of this characteristic in Otx1-/- mice may correspond to an atavism. The same conclusion applies to two other gnathostome-specific characteristics also deleted in Otx1-/- mice, the utriculosaccular duct and the ciliary process. Together with functional analyses of Otx1 and Otx2 genes in mice and comparative analyses of the Otx gene families characterized in chordates, these discoveries lead to the hypothesis that some of the anatomic characteristics of gnathostomes have appeared quite suddenly and almost simultaneously in vertebrate evolution, possibly as a consequence of gene functional diversifications following duplications of an ancestral chordate gene.

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Species referenced: Xenopus
Genes referenced: otx1 otx2