The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age
Open accessAbstract
Parkinson disease affects more than 1% of the population over 60 y old. The dominant models for Parkinson disease are based on the use of chemical toxins to kill dopamine neurons, but do not address the risk factors that normally increase with age. Forkhead transcription factors are critical regulators of survival and longevity. The forkhead transcription factor, foxa2, is specifically expressed in adult dopamine neurons and their precursors in the medial floor plate. Gain- and loss-of-function experiments show this gene, foxa2, is required to generate dopamine neurons during fetal development and from embryonic stem cells. Mice carrying only one copy of the foxa2 gene show abnormalities in motor behavior in old age and an associated progressive loss of dopamine neurons. Manipulating forkhead function may regulate both the birth of dopamine neurons and their spontaneous death, two major goals of regenerative medicine.
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Midbrain dopamine neurons originate from the mesodiencephalic floorplate, a region at the ventral midline defined by Shh+ and Foxa2+ expression.
“These neurons originate from the mesodiencephalic floorplate (FP), a region at the ventral midline defined by the mRNA expression of Shh+ and Foxa2+ [67–73].”
From Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches (2020) · cites this paper as [69]
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- Authors
- Kittappa, R., Chang, W. W., Awatramani, R. B., & McKay, R. D. G.
- Affiliations
- National Institutes of Health (US)
- Northwestern University (US)
- Corresponding author
- McKay, Ronald D. G
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-12-11
- Volume
- 5
- Issue
- 12
- Pages
- e325
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC2121110
- OpenAlex
- W2043269926
- Cited by
- 251
- References
- 53
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 16 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 18 · 2015: 11 · 2014: 20 · 2013: 19 · 2012: 21
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- Michael J. Fox Foundation for Parkinson's Research
- Dana Foundation
- Parkinson's Foundation
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- FOXA2, Parkinson's disease, dopaminergic neurons, neurodegeneration, aging, forkhead transcription factor, neuronal precursors, embryonic stem cells, motor behavior, regenerative medicine
- MeSH terms
- Aging, Animals, Dopamine, Nerve Degeneration, Mice, Knockout, Gene Expression Regulation, Developmental, Parturition, Mice, Hepatocyte Nuclear Factor 3-beta, Hedgehog Proteins
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