The developing lamprey ear closely resembles the zebrafish otic vesicle:otx1expression can account for all major patterning differences

Abstract

The inner ear of adult agnathan vertebrates is relatively symmetric about the anteroposterior axis, with only two semicircular canals and a single sensory macula. This contrasts with the highly asymmetric gnathostome arrangement of three canals and several separate maculae. Symmetric ears can be obtained experimentally in gnathostomes in several ways, including by manipulation of zebrafish Hedgehog signalling, and it has been suggested that these phenotypes might represent an atavistic condition. We have found, however, that the symmetry of the adult lamprey inner ear is not reflected in its early development; the lamprey otic vesicle is highly asymmetric about the anteroposterior axis, both morphologically and molecularly, and bears a striking resemblance to the zebrafish otic vesicle. The single sensory macula originates as two foci of hair cells, and later shows regions of homology to the zebrafish utricular and saccular maculae. It is likely, therefore, that the last common ancestor of lampreys and gnathostomes already had well-defined otic anteroposterior asymmetries. Both lamprey and zebrafish otic vesicles express a target of Hedgehog signalling, patched, indicating that both are responsive to Hedgehog signalling. One significant distinction between agnathans and gnathostomes, however, is the acquisition of otic Otx1 expression in the gnathostome lineage. We show that Otx1 knockdown in zebrafish, as in Otx1 -/-mice, gives rise to lamprey-like inner ears. The role of Otx1 in the gnathostome ear is therefore highly conserved; otic Otx1 expression is likely to account not only for the gain of a third semicircular canal and crista in gnathostomes, but also for the separation of the zones of the single macula into distinct regions.

Identification and developmental expression of two Tbx1/10-related genes in the agnathan Lethenteron japonicum

“…Similar to lampreys, spatially restricted expression of Tbx1 in a posterior domain of the otic epithelium has also been described in zebrafish and mice (Piotrowski et al 2003;Raft et al 2004;Hammond and Whitfield 2006). Recent studies in zebrafish and mouse embryos have shown that Tbx1 plays a crucial role in the developing ear (Jerome and Papaioannou 2001;Piotrowski et al 2003).…”

“…More recently, it has been shown that Tbx1 regulates the growth of a group of otic epithelial cells in the developing ear and then determines their fate (Xu et al 2007). Therefore, Tbx1/10 seems to have gained a novel expression domain and probably a novel function (Hammond and Whitfield 2006) in otic vesicle patterning, before the divergence of lampreys and gnathostomes.…”

Hedgehog Signaling Governs the Development of Otic Sensory Epithelium and Its Associated Innervation in Zebrafish

“…Indeed, Shh Ϫ/ Ϫ mice display a single domain of expression of a marker for utricular, saccular and cochlear epithelia (Riccomagno et al, 2002), a defect comparable to the fusion of macular sensory epithelia described in the zebrafish hh mutants (Hammond et al, 2003) and in the present study. It is not clear whether Hh acts directly on the separation of an initial sensory domain in different sensory epithelia, as in lamprey a single macula communis coexists with apparently active Hh signaling in the otic epithelium (Hammond and Whitfield, 2006). However, it is interesting to note that within this macula communis, anterior and posterior hair cells already develop asynchronously and asymmetrically (Hammond and Whitfield, 2006).…”

“…It is not clear whether Hh acts directly on the separation of an initial sensory domain in different sensory epithelia, as in lamprey a single macula communis coexists with apparently active Hh signaling in the otic epithelium (Hammond and Whitfield, 2006). However, it is interesting to note that within this macula communis, anterior and posterior hair cells already develop asynchronously and asymmetrically (Hammond and Whitfield, 2006). Finally, after emergence of the cochlea during evolution, Shh pathway has been involved in the specification, location and size of the prosensory domain, changes that are thought to correlate with the ability to perceive high frequencies in mammals (Driver et al, 2008).…”

Patterning and morphogenesis of the vertebrate inner ear

“…Interestingly, knockdown of otx1 expression in zebrafish causes failure of the two maculae to separate, similar to the phenotypes described for the Otx1 null mutants. The inner ear morphology of these otx1 knockdown zebrafish embryos also resembles the lamprey inner ears, which do not express otx1 (Hammond and Whitfield, 2006). Thus, it has been proposed that the acquisition of Otx1 expression is an important molecular distinction between agnathans and gnathostomes (Hammond and Whitfield, 2006).…”