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PMID:18076286

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Citation

Kittappa, R, Chang, WW, Awatramani, RB and McKay, RD (2007) The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age. PLoS Biol. 5:e325

Abstract

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.

Links

PubMed PMC2121110 Online version:10.1371/journal.pbio.0050325

Keywords

Aging/physiology; Animals; Dopamine/metabolism; Gene Expression Regulation, Developmental/genetics; Hedgehog Proteins/genetics; Hedgehog Proteins/metabolism; Hepatocyte Nuclear Factor 3-beta/deficiency; Hepatocyte Nuclear Factor 3-beta/genetics; Hepatocyte Nuclear Factor 3-beta/metabolism; Mice; Mice, Knockout; Nerve Degeneration/genetics; Nerve Degeneration/metabolism; Nerve Degeneration/pathology; Parturition/genetics; Parturition/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LMX1B

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GFAP

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NKX22

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:LHX1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PHX2A

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NKX61

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBB3

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:LHX2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GFAP

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SHH

acts_upstream_of_or_within

GO:0001708: cell fate specification

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXA2

acts_upstream_of_or_within

GO:0071542: dopaminergic neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857725

P

Seeded From UniProt

complete

MOUSE:FOXA2

acts_upstream_of_or_within

GO:0008344: adult locomotory behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857725

P

Seeded From UniProt

complete

MOUSE:FOXA2

acts_upstream_of_or_within

GO:0001708: cell fate specification

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:LHX2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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