Ronald D. G. McKay
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Implications For Parkinson’s Sufferers
The gradual loss of dopamine neurons is a hallmark of many neurodegenerative diseases, including especially Parkinson’s.
Restoration of dopamine neurons is one of the goals of both stem cell biology and regenerative medicine.
Perhaps speeding the achievement of that goal is the discovery reported this week in PLoS Biology that the transcription factor FOXA2 plays a central role in the birth and death of dopamine neurons in the midbrain.
By defining precursors of dopamine neurons in the ventral midbrain, Dr. Raja Kittappa, Dr. Wendy Chang, Dr. Rajeshwar Awatramani, and Dr. Ronald McKay of the National Institutes of Health have discovered that dopamine neurons are derived from organizer cells in the floor plate, the ventral cells of the neural tube and the embryonic foundation of the central nervous system.
They also show that FOXA2 specifies the floor plate and actually induces the birth of dopamine neurons.
Mice with only a single copy of the foxa2 gene acquire motor deficits and a late-onset degeneration of dopamine neurons.
This spontaneous cell death preferentially affects neurons associated with Parkinson’s disease.
This work provides new strategies to generate neurons in the laboratory and to block their death in old age.
Citation: Kittappa R, Chang WW, Awatramani RB, McKay RDG (2007) The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age. PLoS Biol 5(12): e325. doi:10.1371/journal.pbio.0050325
Contact: Ronald D.G. McKay, 301-451-8857, mckayr@ninds.nih.gov
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