The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix

•The adhesion GPCR Flamingo/CELSR has an effect on the regulation of body size.•Nematodes lacking the receptors display an increased production of ECM molecules, up and foremost of collagens.•The altered composition of the ECM directly affects cuticle thickness and leads to impaired movement and cuticular function and most like to decreased body size.•Receptor activity involves the PCP molecule VANG-1, but seems independent of the DBL-1/BMP pathway. The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly dynamic. ECM homeostasis is therefore tightly controlled by several mechanisms. Here, we show that FMI-1, the homolog of the Adhesion GPCR Flamingo/CELSR/ADGRC in the nematode Caenorhabditis elegans, modulates the composition of the ECM by controlling the production both of ECM molecules such as collagens and also of ECM modifying enzymes. Thereby, FMI-1 affects the morphology and functionality of the nematode´s cuticle, which is mainly composed of ECM, and also modulates the body size. Mechanistic analyses highlight the fact that FMI-1 exerts its function from neurons non-cell autonomously (trans) solely via its extracellular N terminus. Our data support a model, by which the activity of the receptor, which has a well-described role in the planar cell polarity (PCP) pathway, involves the PCP molecule VANG-1, but seems to be independent of the DBL-1/BMP pathway.