RRC ID 30955
Author Fernandes de Abreu DA, Caballero A, Fardel P, Stroustrup N, Chen Z, Lee K, Keyes WD, Nash ZM, López-Moyado IF, Vaggi F, Cornils A, Regenass M, Neagu A, Ostojic I, Liu C, Cho Y, Sifoglu D, Shen Y, Fontana W, Lu H, Csikasz-Nagy A, Murphy CT, Antebi A, Blanc E, Apfeld J, Zhang Y, Alcedo J, Ch'ng Q.
Title An insulin-to-insulin regulatory network orchestrates phenotypic specificity in development and physiology.
Journal PLoS Genet
Abstract Insulin-like peptides (ILPs) play highly conserved roles in development and physiology. Most animal genomes encode multiple ILPs. Here we identify mechanisms for how the forty Caenorhabditis elegans ILPs coordinate diverse processes, including development, reproduction, longevity and several specific stress responses. Our systematic studies identify an ILP-based combinatorial code for these phenotypes characterized by substantial functional specificity and diversity rather than global redundancy. Notably, we show that ILPs regulate each other transcriptionally, uncovering an ILP-to-ILP regulatory network that underlies the combinatorial phenotypic coding by the ILP family. Extensive analyses of genetic interactions among ILPs reveal how their signals are integrated. A combined analysis of these functional and regulatory ILP interactions identifies local genetic circuits that act in parallel and interact by crosstalk, feedback and compensation. This organization provides emergent mechanisms for phenotypic specificity and graded regulation for the combinatorial phenotypic coding we observe. Our findings also provide insights into how large hormonal networks regulate diverse traits.
Volume 10(3)
Pages e1004225
Published 2014-3-1
DOI 10.1371/journal.pgen.1004225
PMID 24675767
PMC PMC3967928
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Gene Regulatory Networks Insulin / genetics* Insulin / metabolism Longevity / genetics Phenotype Receptor, Insulin / genetics* Receptor, Insulin / metabolism Signal Transduction / genetics Somatomedins / genetics Somatomedins / metabolism
IF 5.175
Times Cited 36
C.elegans tm4467 tm3608 tm3620 tm2560 tm2416 tm2001 tm4144 tm3618 tm3498 tm1053 tm2918 tm4856 tm4886 tm0790 tm0339 tm5155 tm1947 tm5180 tm1875 tm1983 tm1922 tm2988 tm2632 tm2308