Evidence map›Paper›PMID 27354364›Full record

ArticleThe EMBO journal2016

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease.

J Carlos Villaescusa, Bingsi Li, Enrique M Toledo, Pia Rivetti di Val Cervo, Shanzheng Yang, Simon Rw Stott, Karol Kaiser, Saiful Islam, Daniel Gyllborg, Rocio Laguna-Goya and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 116 citations in OpenAlex.

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18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 4 countries.

J Carlos VillaescusaLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic Psychiatric Stem Cell Group, Neurogenetics Unit, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Bingsi LiDepartment of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY, USA.
Enrique M ToledoLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Pia Rivetti di Val CervoLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Shanzheng YangLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Simon Rw StottJohn van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Karol KaiserLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Saiful IslamLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Daniel GyllborgLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Rocio Laguna-GoyaJohn van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Michael LandrehDivision of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics Karolinska Institutet, Stockholm, Sweden.
Peter LönnerbergLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Anna FalkDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Tomas BergmanDivision of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics Karolinska Institutet, Stockholm, Sweden.
Roger A BarkerJohn van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Sten LinnarssonLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Licia SelleriDepartment of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY, USA.
Ernest ArenasLaboratory of Molecular Neurobiology, DBRM, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden ernest.arenas@ki.se.ORCID 0000-0003-0197-6577
Karolinska Institutet · SEUniversity of Cambridge · GBCornell University · USKarolinska University Hospital · SEMasaryk University · CZ

Funding

Pbx-Directed Control of Cellular Behaviors that Drive Midface MorphogenesisR01DE024745 · NIDCR · WEILL MEDICAL COLL OF CORNELL UNIV · PI SELLERI, LICIA · 2015 to 2025
$5.1M
Mechanisms of Pbx-directed Genetic &Transcriptional Control of Limb DevelopmentR01HD043997 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI SELLERI, LICIA · 2004 to 2016
$3.7M
Medical Research Council MC_PC_12009NICHD NIH HHS R01 HD043997NIDCR NIH HHS R01 DE024745
6 · The paper itself

Abstract

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. Thus, our results reveal novel roles for PBX1 and its transcriptional network in mDAn development and PD, opening the door for new therapeutic interventions.

Indexed as

Cell DifferentiationGene Regulatory NetworksDNA-Binding ProteinsDopaminergic NeuronsHumansParkinson DiseasePre-B-Cell Leukemia Transcription Factor 1Proto-Oncogene ProteinsSubstantia NigraDNA-Binding ProteinsPBX1 protein, humanPre-B-Cell Leukemia Transcription Factor 1Proto-Oncogene ProteinsChIP‐Seqdopaminedopaminergic differentiationmesencephalonstem cells

Identifiers

PMID27354364
PMCPMC5282836
OpenAlexW2470046319

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.