09-P074 A functional characterisation of Mospd 1 in cardiac development

the function of genes coding for transmembrane ion channels and transporters expressed in specialised cells of the cochlea and vestibule. We have characterised the expression patterns of zebrafish genes orthologous to those involved in endolymph production in the mammal and find that the major site of expression of these genes in the developing ear is in the epithelial projections that form the semicircular canal system. The endolymphatic duct is a small structure in the zebrafish ear, but nevertheless develops according to a conserved developmental programme, similar to that in the mammal. We have identified foxi1 as a robust marker of this structure in the zebrafish. We describe a series of mutants that display an abnormality in ear volume. In kei and cc59.3a, the lumen of the otic vesicle is distended from early stages. In lte, endolymph volume is initially normal but later decreases dramatically. A disruption of endolymph homeostasis may also contribute to the abnormalities in ear size found in mutants with other otic patterning defects, especially those with semicircular canal defects (bge/lau, cls/sox10, hph, vgo/tbx1), or where the endolymphatic duct develops abnormally (cls/sox10, noi/pax2a, val/ mafb, vgo/tbx1). The expression of endolymph-generating ion channel genes in the epithelial projections of the ear is disrupted in several of these mutants. We conclude that the zebrafish embryo may provide a useful model of human endolymph disorders.