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FoxP1 promotes midbrain identity in embryonic stem cell-derived dopamine neurons by regulating Pitx3

Konstantoulas, Constantine James; Parmar, Malin LU and Li, Meng (2010) In Journal of Neurochemistry 113(4). p.836-847
Abstract
P>The robust generation of midbrain dopamine neurons from embryonic stem cells and patient-specific induced pluripotent stem cells is a prospective tool for the development of new drugs and cell based therapies, and investigations into the aetiology of Parkinson's disease. To achieve this, it is crucial to identify the fate-determining regulatory factors that influence dopamine cell fate decision and the underlying molecular machinery. We identified FoxP1 as a novel marker for midbrain dopamine neurons. Enforced expression of FoxP1 in embryonic stem cells actuates the expression of Pitx3, a homeobox protein that is exclusively expressed in midbrain dopaminergic neurons and is required for their differentiation and survival during... (More)
P>The robust generation of midbrain dopamine neurons from embryonic stem cells and patient-specific induced pluripotent stem cells is a prospective tool for the development of new drugs and cell based therapies, and investigations into the aetiology of Parkinson's disease. To achieve this, it is crucial to identify the fate-determining regulatory factors that influence dopamine cell fate decision and the underlying molecular machinery. We identified FoxP1 as a novel marker for midbrain dopamine neurons. Enforced expression of FoxP1 in embryonic stem cells actuates the expression of Pitx3, a homeobox protein that is exclusively expressed in midbrain dopaminergic neurons and is required for their differentiation and survival during development and from embryonic stem cells in vitro. We show that FoxP1 can be recruited to the Pitx3 locus in embryonic stem cells and regulate Pitx3 promoter activity in a dual-luciferase assay. This transcriptional regulation of Pitx3 by FoxP1 depends on the presence of two high affinity binding sites in the distal Pitx3 promoter, through which FoxP1 directly binds as demonstrated by chromatin immunoprecipitation and electrophoretic mobility shift assay. Thus, this study demonstrates for the first time a transcription regulatory role for FoxP1 on the Pitx3 gene in mammalian stem cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
transcription, transcription factor 3, paired-like homeodomain, forkhead box P1, midbrain dopaminergic neurons
in
Journal of Neurochemistry
volume
113
issue
4
pages
836 - 847
publisher
Wiley-Blackwell
external identifiers
  • wos:000276656100004
  • scopus:77950941894
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2010.06650.x
language
English
LU publication?
yes
id
c35aa289-4283-450a-890c-5c9a99e38fb7 (old id 1602979)
date added to LUP
2010-05-19 10:06:45
date last changed
2018-05-29 12:32:12
@article{c35aa289-4283-450a-890c-5c9a99e38fb7,
  abstract     = {P>The robust generation of midbrain dopamine neurons from embryonic stem cells and patient-specific induced pluripotent stem cells is a prospective tool for the development of new drugs and cell based therapies, and investigations into the aetiology of Parkinson's disease. To achieve this, it is crucial to identify the fate-determining regulatory factors that influence dopamine cell fate decision and the underlying molecular machinery. We identified FoxP1 as a novel marker for midbrain dopamine neurons. Enforced expression of FoxP1 in embryonic stem cells actuates the expression of Pitx3, a homeobox protein that is exclusively expressed in midbrain dopaminergic neurons and is required for their differentiation and survival during development and from embryonic stem cells in vitro. We show that FoxP1 can be recruited to the Pitx3 locus in embryonic stem cells and regulate Pitx3 promoter activity in a dual-luciferase assay. This transcriptional regulation of Pitx3 by FoxP1 depends on the presence of two high affinity binding sites in the distal Pitx3 promoter, through which FoxP1 directly binds as demonstrated by chromatin immunoprecipitation and electrophoretic mobility shift assay. Thus, this study demonstrates for the first time a transcription regulatory role for FoxP1 on the Pitx3 gene in mammalian stem cells.},
  author       = {Konstantoulas, Constantine James and Parmar, Malin and Li, Meng},
  issn         = {1471-4159},
  keyword      = {transcription,transcription factor 3,paired-like homeodomain,forkhead box P1,midbrain dopaminergic neurons},
  language     = {eng},
  number       = {4},
  pages        = {836--847},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {FoxP1 promotes midbrain identity in embryonic stem cell-derived dopamine neurons by regulating Pitx3},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2010.06650.x},
  volume       = {113},
  year         = {2010},
}