1. Academic Validation
  2. Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans

Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans

  • Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4065-E4074. doi: 10.1073/pnas.1617392114.
Elien Van Sinay 1 Olivier Mirabeau 2 Geert Depuydt 1 Matthias Boris Van Hiel 1 Katleen Peymen 1 Jan Watteyne 1 Sven Zels 1 Liliane Schoofs 3 Isabel Beets 3
Affiliations

Affiliations

  • 1 Functional Genomics and Proteomics Group, Department of Biology, KU Leuven, 3000 Leuven, Belgium.
  • 2 Genetics and Biology of Cancers Unit, Institut Curie, INSERM U830, Paris Sciences et Lettres Research University, Paris 75005, France.
  • 3 Functional Genomics and Proteomics Group, Department of Biology, KU Leuven, 3000 Leuven, Belgium; liliane.schoofs@kuleuven.be isabel.beets@kuleuven.be.
Abstract

In vertebrates thyrotropin-releasing hormone (TRH) is a highly conserved neuropeptide that exerts the hormonal control of thyroid-stimulating hormone (TSH) levels as well as neuromodulatory functions. However, a functional equivalent in protostomian Animals remains unknown, although TRH receptors are conserved in proto- and deuterostomians. Here we identify a TRH-like neuropeptide precursor in Caenorhabditis elegans that belongs to a bilaterian family of TRH precursors. Using CRISPR/Cas9 and RNAi reverse genetics, we show that TRH-like neuropeptides, through the activation of their receptor TRHR-1, promote growth in Celegans TRH-like Peptides from pharyngeal motor neurons are required for normal body size, and knockdown of their receptor in pharyngeal muscle cells reduces growth. Mutants deficient for TRH signaling have no defects in pharyngeal pumping or isthmus peristalsis rates, but their growth defect depends on the Bacterial diet. In addition to the decrease in growth, trh-1 mutants have a reduced number of offspring. Our study suggests that TRH is an evolutionarily ancient neuropeptide, having its origin before the divergence of protostomes and deuterostomes, and may ancestrally have been involved in the control of postembryonic growth and reproduction.

Keywords

C. elegans; growth regulation; molecular evolution; neuropeptide; thyrotropin-releasing hormone.

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