Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans

Significance

The hypothalamic neuropeptide TRH (thyrotropin-releasing hormone) is one of the major endocrine factors that regulate vertebrate physiology. For decades the general assumption has been that TRH neuropeptides are not present in protostomes, at least not in ecdysozoans, despite the presence of TRH receptor orthologs in these phyla. Here we identify a TRH-related neuropeptide–receptor pathway in the nematode Caenorhabditis elegans . TRH-like neuropeptides activate the C . elegans TRH receptor ortholog in cell-culture cells. Using RNAi and CRISPR/Cas9 reverse genetics, we discovered that TRH-related signaling in the pharyngeal system promotes C . elegans growth. Our study provides evidence of a functional TRH neuropeptide–receptor pathway in invertebrates, suggesting that TRH signaling had evolved in a bilaterian ancestor more than 700 million years ago.