@article{171b31dcb8ea44bdb90bc965f757428b,
title = "Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions",
abstract = "The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothalamus is an essential part of the hypothalamic-pituitary-adrenal axis and regulates the fight-or-flight response, and thus, we hypothesized that selective breeding for tameness/aggressiveness has shaped the hypothalamic transcriptomic profile. RNA-seq analysis identified 70 differentially expressed genes (DEGs). Seven of these genes, DKKL1, FBLN7, NPL, PRIMPOL, PTGRN, SHCBP1L and SKIV2L, showed the same direction expression differences in the hypothalamus, basal forebrain and prefrontal cortex. The genes differentially expressed across the three tissues are involved in cell division, differentiation, adhesion and carbohydrate processing, suggesting an association of these processes with selective breeding. Additionally, 159 transcripts from the hypothalamus demonstrated differences in the abundance of alternative spliced forms between the tame and aggressive foxes. Weighted gene coexpression network analyses also suggested that gene modules in hypothalamus were significantly associated with tame vs aggressive behavior. Pathways associated with these modules include signal transduction, interleukin signaling, cytokine-cytokine receptor interaction and peptide ligand-binding receptors (eg, G-protein coupled receptor [GPCR] ligand binding). Current studies show the selection for tameness vs aggressiveness in foxes is associated with unique hypothalamic gene profiles partly shared with other brain regions and highlight DEGs involved in biological processes such as development, differentiation and immunological responses. The role of these processes in fox and dog domestication remains to be determined.",
keywords = "RNA-seq, behavior, brain, breeding, canine, dog, domestication, evolutionary selection, genetics, hypothalamus",
author = "Rosenfeld, {Cheryl S.} and Hekman, {Jessica P.} and Johnson, {Jennifer L.} and Zhen Lyu and Ortega, {Madison T.} and Trupti Joshi and Jiude Mao and Vladimirova, {Anastasiya V.} and Gulevich, {Rimma G.} and Kharlamova, {Anastasiya V.} and Acland, {Gregory M.} and Hecht, {Erin E.} and Xu Wang and Clark, {Andrew G.} and Trut, {Lyudmila N.} and Behura, {Susanta K.} and Kukekova, {Anna V.}",
note = "information Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Grant/Award Number: 0324-2018-0016; Jonathan Baldwin Turner Scholarship Program; National Institute of Environmental Health Sciences, Grant/Award Number: R01ES025547; National Institutes of Health, Grant/Award Numbers: GM120782, R25GM056901; Russian Scientific Foundation, Grant/Award Number: 16-14-10216; U.S. Department of Agriculture, Grant/Award Number: 538922; University of IllinoisWe thank Irina V. Pivovarova, Tatyana I. Semenova, Eugene A. Martinov and all the animal keepers at the Institute of Cytology and Genetics (ICG) experimental farm for research assistance. This project was supported by NIH R01 ES025547 (to C. S. R.), NIH GM120782 (to A. V. K.), USDA Federal Hatch Project (to A. V. K.), a Campus Research Board grant from the University of Illinois at Urbana-Champaign (to A. V. K.), the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (grant number 0324-2019-0041), the Jonathan Baldwin Turner Scholarship Program and Dr. Temple Grandin (to J. P. H.) and IMSD-EXPRESS program (R25GM056901, to M. T. O.). We appreciate Donald L. Connor's assistance with figure preparation and Dr Wes Warren's input for the informatics analyses. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. The data used for the analyses described in this manuscript were obtained from GTEx Multi Gene Query on the GTEx Portal (V8) on 03/19/19 and used to generate Figure B. B. We thank Irina V. Pivovarova, Tatyana I. Semenova, Eugene A. Martinov and all the animal keepers at the Institute of Cytology and Genetics (ICG) experimental farm for research assistance. This project was supported by NIH R01 ES025547 (to C. S. R.), NIH GM120782 (to A. V. K.), USDA Federal Hatch Project (to A. V. K.), a Campus Research Board grant from the University of Illinois at Urbana‐Champaign (to A. V. K.), the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (grant number 0324‐2019‐0041), the Jonathan Baldwin Turner Scholarship Program and Dr. Temple Grandin (to J. P. H.) and IMSD‐EXPRESS program (R25GM056901, to M. T. O.). We appreciate Donald L. Connor's assistance with figure preparation and Dr Wes Warren's input for the informatics analyses. The Genotype‐Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. The data used for the analyses described in this manuscript were obtained from GTEx Multi Gene Query on the GTEx Portal (V8) on 03/19/19 and used to generate Figure",
year = "2020",
month = jan,
day = "1",
doi = "10.1111/gbb.12614",
language = "English (US)",
volume = "19",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
publisher = "Wiley-Blackwell",
number = "1",
}