The FMRFamide-like peptide FLP-11 regulates the production and secretion of the 1 TGF-β-like protein DAF-7 during Caenorhabditis elegans larval development

FMRFamide-like peptides (FLPs) are widely conserved in nematodes. Here, we conducted a molecular genetic study to confirm that the flp-11 gene regulates larval development in the free-living soil nematode model species Caenorhabditis elegans. We demonstrated that: 1) FLP-11 suppresses larval development, resulting in dauer diapause; 2) the production and secretion of FLP-11 by specific neurons is modulated by the availability of food (e.g., Escherichia coli) and by population density, both of which determine larval development/dauer diapause via transforming growth factor-β (TGF-β)-like and insulin-like signaling; 3) the FLP-11 peptide reduces the production and secretion of DAF-7, the sole TGF-β-like protein involved in larval development; 4) FLP-11 is not involved in insulin-like signaling; 5) FLP-11 modulates dauer diapause via neuropeptide receptor-22 (NPR-22), which regulates DAF-7 production and secretion. This study is the first to describe an important short neuropeptide that directly regulates a TGF-β-like protein via its receptor candidate, thereby influencing larval development.