The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age

Raja Kittappa, Wendy W. Chang, Rajeshwar B. Awatramani, Ronald D G McKay

Research output: Contribution to journalArticle

177 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2875-2884
Number of pages10
JournalPLoS biology
Volume5
Issue number12
DOIs
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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