Body axis elongation and ciliary function in zebrafish require Noni a novel ciliary protein

摘要

Cilia are highly conserved structures found from protozoato mammals where they play major functions in motilityand sensation. Ciliary dysfunction leads to a variety ofhuman genetic diseases called ciliopathies. RFX transcriptionfactors are key players in regulating genes involved incilia assembly from C. elegans to mammals. Using a genomicscreen to identify targets of RFX, we selected a novelgene, noni, potentially implicated in cilia biology. Noknown function has been described for this gene, which ishighly conserved and specific of ciliated species. We showthat noni expression is increased during in vitro inducedciliogenesis in primary mouse ependymal cell culture andthat Noni localizes to cilia from Drosophila to mammals.We performed functional analysis in zebrafish and showthat loss of function of noni mimics human symptomsassociated with ciliopathies such as kidney cysts and randomizedleft right patterning. We demonstrate that Noni isnecessary for cilia function. Indeed, we show that nodalflow is impaired in Kupffer’s vesicle of noni morphants.Moreover, noni morphants have defects in body axis elongationand present impaired basal body positioning in thefloor plate suggesting that noni is implicated in planar cellpolarity (PCP). To test this hypothesis, we are currentlyanalysing genetic interaction with known PCP componentsassociated with cilia function. In conclusion, we have identifieda novel conserved ciliary gene noni, which is necessaryfor ciliary function and planar cell polarity in zebrafish.