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.
Highlights
The Wfs1 gene encodes wolframin, an endoplasmic reticulum (ER)-resident membrane protein whose functions include the regulation of insulin production and secretion from pancreatic β-cells, as well as the regulation of ER stress response, cellular Ca2+ homeostasis, and secretory granule acidification [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
In the ventral tegmental area (VTA), another source of dopaminergic fibres that terminate in the ventral striatum and frontal cortex, we detected weak diffuse expression of Wfs1, the sparse cells expressing Drd1a and stronger diffuse expression of Drd5 (Fig 1M, 1N and 1O)
Wfs1 is a gene encoding Wolframin, a protein involved in mitigating ER stress, regulating insulin secretion from pancreatic β-cells, coordinating cellular Ca2+ homeostasis, and stabilizing the folding of several proteins
Summary
The Wfs gene encodes wolframin, an ER-resident membrane protein whose functions include the regulation of insulin production and secretion from pancreatic β-cells, as well as the regulation of ER stress response, cellular Ca2+ homeostasis, and secretory granule acidification [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. Loss of functional WFS1 protein results in Wolfram syndrome, characterized by PLOS ONE | DOI:10.1371/journal.pone.0172825. Relation of Wfs and D1-type dopamine receptors in amniote brain the Ministry of Education and Research (SF0180019s11) (www.hm.ee); European Union through the European Regional Development Fund (Competence Centre on Health Technology, EU48695) (www.eas.ee); National Science Foundation (www.nsf.gov) Grant IOS 145177 to SFG; and Centre of Excellence in Genomics and Translational Medicine, University of Tartu, funded by the European Union through the European Regional Development Fund (Project No 20142020.4.01.15-0012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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