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Wfs1在羊膜动物大脑的多巴胺感受区域表达,并调节D1样受体的水平。

Wfs1 is expressed in dopaminoceptive regions of the amniote brain and modulates levels of D1-like receptors.

作者信息

Tekko Triin, Lakspere Triin, Allikalt Anni, End Jaanus, Kõlvart Karl Rene, Jagomäe Toomas, Terasmaa Anton, Philips Mari-Anne, Visnapuu Tanel, Väärtnõu Fred, Gilbert Scott F, Rinken Ago, Vasar Eero, Lilleväli Kersti

机构信息

Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.

Centre of Excellence in Genomics and Translational Medicine, University of Tartu, Tartu, Estonia.

出版信息

PLoS One. 2017 Mar 7;12(3):e0172825. doi: 10.1371/journal.pone.0172825. eCollection 2017.

Abstract

During amniote evolution, the construction of the forebrain has diverged across different lineages, and accompanying the structural changes, functional diversification of the homologous brain regions has occurred. This can be assessed by studying the expression patterns of marker genes that are relevant in particular functional circuits. In all vertebrates, the dopaminergic system is responsible for the behavioral responses to environmental stimuli. Here we show that the brain regions that receive dopaminergic input through dopamine receptor D1 are relatively conserved, but with some important variations between three evolutionarily distant vertebrate lines-house mouse (Mus musculus), domestic chick (Gallus gallus domesticus) / common quail (Coturnix coturnix) and red-eared slider turtle (Trachemys scripta). Moreover, we find that in almost all instances, those brain regions expressing D1-like dopamine receptor genes also express Wfs1. Wfs1 has been studied primarily in the pancreas, where it regulates the endoplasmic reticulum (ER) stress response, cellular Ca2+ homeostasis, and insulin production and secretion. Using radioligand binding assays in wild type and Wfs1-/- mouse brains, we show that the number of binding sites of D1-like dopamine receptors is increased in the hippocampus of the mutant mice. We propose that the functional link between Wfs1 and D1-like dopamine receptors is evolutionarily conserved and plays an important role in adjusting behavioral reactions to environmental stimuli.

摘要

在羊膜动物进化过程中,前脑结构在不同谱系中发生了分化,伴随着结构变化,同源脑区出现了功能多样化。这可以通过研究特定功能回路中相关标记基因的表达模式来评估。在所有脊椎动物中,多巴胺能系统负责对环境刺激的行为反应。在此我们表明,通过多巴胺受体D1接受多巴胺能输入的脑区相对保守,但在三个进化距离较远的脊椎动物品系——家鼠(小家鼠)、家鸡(原鸡家鸡亚种)/普通鹌鹑(日本鹌鹑)和红耳龟(滑龟)之间存在一些重要差异。此外,我们发现几乎在所有情况下,那些表达D1样多巴胺受体基因的脑区也表达Wfs1。Wfs1主要在胰腺中被研究,它在胰腺中调节内质网(ER)应激反应、细胞钙稳态以及胰岛素的产生和分泌。通过在野生型和Wfs1基因敲除小鼠脑内进行放射性配体结合试验,我们发现突变小鼠海马体中D1样多巴胺受体的结合位点数量增加。我们提出,Wfs1与D1样多巴胺受体之间的功能联系在进化上是保守的,并且在调节对环境刺激的行为反应中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c103/5436468/f199bf0e305c/pone.0172825.g001.jpg

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