LAUSR

through modulation of the Glis. RNF220 is specifically expressed in the ventral neural tube and knockout of RNF220 leads to ventral expansion of the medial V1 cells, dorsal expansion of the ventral V3 cells and loss of the V2 cells, suggesting increased activities of both the repressor and activator forms of the Glis. We showed that RNF220 interacts with all Glis, induces their K63-linked ubiquitination and increases their distribution in the insoluble cytoskeleton fraction. K63-linked ubiquitination of Glis promotes their interaction with HDAC6, an ubiquitin-binding and microtubuleassociated deacetylase, which are then recruited to microtubules. In this way, a large fraction of Glis are sequestered from further procession or function, which greatly affects the shape of the Gli gradient. Our work revealed a novel mechanism for the shaping of gradient mediated by specific ubiquitination and sequestration.