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Proc Natl Acad Sci U S A. 2009 May 5;106(18):7613-8. doi: 10.1073/pnas.0902396106. Epub 2009 Apr 21.

Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells.

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  • 1The Ludwig Institute for Cancer Research, Karolinska Institutet, 17177 Stockholm, Sweden.

Erratum in

  • Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21229.

Abstract

Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease.

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