The large cadherin Fat and its ligand Dachsous (Ds) control the growth and planar polarity of developing tissues. Now, Kenneth Irvine and co-workers shed light on how they are regulated by identifying a conserved cytoplasmic protein, Lowfat (Lft), as a Fat signalling modulator in Drosophila(see p. 3223). lft mutant flies have shortened wings, a trait typical for Fat pathway defects; when they are crossed with either fat or dsmutants, these wing defects worsen. Lft binds to the cytoplasmic domains of Ds and Fat, the authors show, and Fat and Ds levels are decreased in lftmutants, but increased by lft overexpression, indicating that lft modulates Fat signalling through post-transcriptional regulation. Furthermore, the human Lft homologues, LIX1 and LIX1-L, bind to the human Fat homologue FAT4. The authors propose, therefore, that Lft is a highly conserved modulator of Fat signalling. Since LIX1 is also linked to spinal muscular atrophy, future studies of Lft might also be important for understanding human disease.

© 2009.
2009