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

Konstantoulas, Constantine James, Parmar, Malin and Li, Meng ORCID: https://orcid.org/0000-0002-4803-4643 2010. FoxP1 promotes midbrain identity in embryonic stem cell-derived dopamine neurons by regulating Pitx3. Journal of Neurochemistry 113 (4) , pp. 836-847. 10.1111/j.1471-4159.2010.06650.x

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	forkhead box P1; midbrain dopaminergic neurons; paired-like homeodomain transcription factor 3; transcription
Publisher:	Wiley-Blackwell
ISSN:	0022-3042
Last Modified:	24 Oct 2022 10:57
URI:	https://orca.cardiff.ac.uk/id/eprint/46520

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