A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson’s disease
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F16%3A00090372" target="_blank" >RIV/00216224:14310/16:00090372 - isvavai.cz</a>
Result on the web
<a href="http://emboj.embopress.org/content/embojnl/early/2016/06/28/embj.201593725.full.pdf" target="_blank" >http://emboj.embopress.org/content/embojnl/early/2016/06/28/embj.201593725.full.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/embj.201593725" target="_blank" >10.15252/embj.201593725</a>
Alternative languages
Result language
angličtina
Original language name
A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson’s disease
Original language description
Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human stem cells. Mechanistically, PBX1 plays a dual role in transcription by directly repressing or activating genes, such as Onecut2 to inhibit lateral fates during embryogenesis, Pitx3 to promote mDAn development, and Nfe2l1 to protect from oxidative stress. Notably, PBX1 and NFE2L1 levels are severely reduced in dopaminergic neurons of the substantia nigra of Parkinson’s disease (PD) patients and decreased NFE2L1 levels increases damage by oxidative stress in human midbrain cells.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EC - Immunology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/EE2.3.20.0180" target="_blank" >EE2.3.20.0180: Cooperation between Masaryk University and Karolinska Institutet, Stockholm in the field of biomedicine</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
The EMBO Journal
ISSN
0261-4189
e-ISSN
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Volume of the periodical
35
Issue of the periodical within the volume
18
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
1963-1978
UT code for WoS article
000384084900003
EID of the result in the Scopus database
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