Qiu, J;
McQueen, J;
Bilican, B;
Dando, O;
Magnani, D;
Punovuori, K;
Selvaraj, BT;
... Hardingham, GE; + view all
(2016)
Evidence for evolutionary divergence of activity-dependent gene expression in developing neurons.
eLife
, 2016
(5)
, Article e20337. 10.7554/eLife.20337.
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Abstract
Evolutionary differences in gene regulation between humans and lower mammalian experimental systems are incompletely understood, a potential translational obstacle that is challenging to surmount in neurons, where primary tissue availability is poor. Rodent-based studies show that activity-dependent transcriptional programs mediate myriad functions in neuronal development, but the extent of their conservation in human neurons is unknown. We compared activity-dependent transcriptional responses in developing human stem cell-derived cortical neurons with those induced in developing primary- or stem cell-derived mouse cortical neurons. While activity-dependent gene-responsiveness showed little dependence on developmental stage or origin (primary tissue vs. stem cell), notable species-dependent differences were observed. Moreover, differential species-specific gene ortholog regulation was recapitulated in aneuploid mouse neurons carrying human chromosome-21, implicating promoter/enhancer sequence divergence as a factor, including human-specific activity-responsive AP-1 sites. These findings support the use of human neuronal systems for probing transcriptional responses to physiological stimuli or indeed pharmaceutical agents.
| Type: | Article |
|---|---|
| Title: | Evidence for evolutionary divergence of activity-dependent gene expression in developing neurons |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.20337 |
| Publisher version: | http://dx.doi.org/10.7554/eLife.20337 |
| Language: | English |
| Additional information: | Copyright © Qiu et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | science & technology, life sciences & biomedicine, biology, life sciences & biomedicine - other topics, cortical-neurons, nervous-system, stem-cells, c-fos, calcium, transcription, neuroprotection, mechanisms, binding, CREB |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1519967 |
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