the foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old agefoxa2基因控制多巴胺神经元的出生和自发的退化.pdf

PLoS BIOLOGY The foxa2 Gene Controls the Birth and Spontaneous Degeneration of Dopamine Neurons in Old Age 1[ 1[ 2 1* Raja Kittappa , Wendy W. Chang , Rajeshwar B. Awatramani , Ronald D. G. McKay 1 Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Department of Neurology, Northwestern University School of Medicine, Chicago, Illinois, United States of America 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. 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 Introduction