The CELSR/Flamingo homolog FMI-1 is well known for its key role in planar cell polarity (PCP) and axon guidance. The Adhesion-G protein-coupled receptor (aGPCR) acts as one of the PCP core proteins besides Frizzled, Dishevelled, Diego, Van Gogh or Prickle to realize the polarization of tissues such as epithelia. Interestingly, few studies report that aGPCRs as well as parts of the PCP core pathway components have also implications in other processes such as the regulation of metabolic processes. Here, we show that FMI-1 is involved in body size regulation. Characterizing two different
fmi-1 loss-of-function mutants we observed a significantly smaller body size, a prolonged lifespan, higher fat levels, and abnormal movement in the mutants compared to wild-type animals. None of these phenotypes was caused by caloric restriction or defects in food intake. Transcriptome analyses revealed that a large number of collagen gens are significantly upregulated in the absence of FMI-1. This was verified by directly assessing collagen in the worms. We found that body size is regulated by FMI-1 exerting a signal from sensory neurons, thereby affecting hypodermal collagen synthesis. However, the respective phenotypes of
fmi-1 mutants are not a consequence of the previously described neuronal mismigration. Rescue experiments revealed that this function of FMI-1 is dependent solely on the N terminus of the GPCR, and thus, not on classical intracellular signaling into the same cell. Functional and expression analyses showed that FMI-1 signals are dependent on components of the insulin/IGF-1-like signaling pathway such as the DAF-16/FoxO transcription factor. Further, we tested a relation to the BMP signalling pathway. Interestingly, the role of FMI-1 in body size regulation seems to be caused by a different mechanism than its function in fat storage. We hypothesize that the lack of the FMI-1 leads to higher levels of collagen in the worms' cuticle, restricting its growth and movement and making it more resistant towards external stress. Taking together, our data highly suggest the PCP molecule Flamingo to be an interesting player in collagen homeostasis and body size regulation.