Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

We investigated the development of inner ear innervation in Otx1 null mutan ts, which lack a horizontal canal, between embryonic day 12 (E12) and postn atal day 7 (P7) with Dil and immunostaining for acetylated tubulin. Compara ble to control animals, horizontal crista-like fibers were found to cross o ver the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 nu ll mutants had a small patch of sensory hair cells at this position. Measur ement of the area of the utricular macula suggested it to be enlarged in Ot x1 null mutants. We suggest that parts of the horizontal canal crista remai n incorporated in the utricular sensory epithelium in Otx1 null mutants. Ot her parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajecto ry as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the do rsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 i s not directly involved in sensory hair cell formation of the horizontal ca nal but affects the segregation of the horizontal canal crista from the utr icle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal c anal morphogenesis as well as morphogenesis of these foramina.