Mice with the fused toes (Ft) mutation - a 1.6 Mb chromosomal deletion encompassing six genes - exhibit phenotypes reminiscent of disrupted Hedgehog (Hh) signalling. Vierkotten et al. have individually knocked out these genes in mice to identify which one is involved in Hh signalling. On , they reveal that the loss of fantom (Ftm) accounts for most defects in Ft mice. Importantly, they report that Ftm localises to the ciliary basal body where it functions as a novel component of cilia-related Hh signalling - regulating the Gli3 activator (Gli3A) to processed Gli3 repressor(Gli3R) ratio (Gli transcription factors act downstream of Hh). In Ftm mutant mice, Gli3 levels increase; however, it remains unprocessed, altering the ratio of Gli3A:Gli3R and consequently Hh transcriptional output. Interestingly, Ftm is not required for cilia assembly;however, cilia numbers are reduced where morphogenetic processes occur and thus cilia-coupled signalling might be required for cilia maintenance. In Drosophila, Hh signalling occurs independently of cilia;unsurprisingly, a fly Ftm homologue hasn't been identified.
