@article {528676,
	title = {An insulin-to-insulin regulatory network orchestrates phenotypic specificity in development and physiology},
	journal = {^co-corresponding author; PLoS Genet},
	volume = {10},
	number = {3},
	year = {2014},
	note = {<p>
	Fernandes de Abreu, Diana AndreaCaballero, AntonioFardel, PascalStroustrup, NicholasChen, ZhunanLee, KyunghwaKeyes, William DNash, Zachary MLopez-Moyado, Isaac FVaggi, FedericoCornils, AstridRegenass, MartinNeagu, AncaOstojic, IvanLiu, ChangCho, YongminSifoglu, DenizShen, YuFontana, WalterLu, HangCsikasz-Nagy, AttilaMurphy, Coleen TAntebi, AdamBlanc, EricApfeld, JavierZhang, YunAlcedo, JoyCh{\textquoteright}ng, QueelimengDP2 OD004402-01/OD/NIH HHS/P40 OD010440/OD/NIH HHS/R01 AG034994/AG/NIA NIH HHS/R01 DC009852/DC/NIDCD NIH HHS/R01AG035317/AG/NIA NIH HHS/R01GM088333/GM/NIGMS NIH HHS/R03 AG032481/AG/NIA NIH HHS/R21EB012803/EB/NIBIB NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2014/03/29 06:00PLoS Genet. 2014 Mar 27;10(3):e1004225. doi: 10.1371/journal.pgen.1004225. eCollection 2014 Mar.
</p>
},
	month = {Mar},
	pages = {e1004225},
	abstract = {<p>
	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.
</p>
},
	keywords = {Animals, Caenorhabditis elegans Proteins/*genetics, Caenorhabditis elegans/*genetics/growth \& development, Gene Regulatory Networks, Insulin/*genetics/metabolism, Longevity/genetics, Phenotype, Receptor, Insulin/*genetics/metabolism, Signal Transduction/genetics, Somatomedins/genetics/metabolism},
	isbn = {1553-7404 (Electronic)1553-7390 (Linking)},
	author = {* Fernandes de Abreu, D. A. and Caballero, A. and Fardel, P. and Stroustrup, N. and Chen, Z. and Lee, K. and Keyes, W. D. and Nash, Z. M. and Lopez-Moyado, I. F. and Vaggi, F. and Cornils, A. and Regenass, M. and Neagu, A. and Ostojic, I. and Liu, C. and Cho, Y. and Sifoglu, D. and Shen, Y. and Fontana, W. and Lu, H. and Csikasz-Nagy, A. and Murphy, C. T. and Antebi, A.^ and Blanc, E.^ and Apfeld, J.^ and Zhang, Y.^ and Alcedo, J.^ and Ch{\textquoteright}ng, Q.^}
}
