Related Articles The Role of Lmx1a in the Differentiation of Human Embryonic Stem Cells into Midbrain Dopamine Neurons in Culture and after Transplantation into a Parkinson's Disease Model. Stem Cells. 2008 Oct 2; Authors: Cai J, Donaldson A, Yang M, German MS, Enikolopov G, Iacovitti L Recent studies have provided important insight into the homeoprotein Lmx1a and its role in the commitment of cells to a midbrain dopamine (mDA) fate in the developing mouse. We show here that Lmx1a also plays a pivotal role in the mDA differentiation of human embryonic stem (hES) cells. Thus, as indicated by siRNA experiments, the transient early expression of Lmx1a is necessary for the coordinated expression of all other DA-specific phenotypic traits as hES cells move from multipotent neural progenitors (hNPs) to more restricted precursor cells in vitro. Moreover, only Lmx1a-specified hNPs have the potential to differentiate into bona fide midbrain mDA neurons after transplantation into the 6-hydroxydopamine treated rat striatum. In contrast, cortical HNPCs and mouse SVZ cells do not express Lmx1a or become mDA neurons even when placed in an environment that fosters their DA differentiation in vitro or in vivo. These findings suggest that Lmx1a may be critical to the development of mDA neurons from hES cells and, that along with other key early DA markers (Aldh1a1), may prove to be extremely useful for the selection of appropriately staged and suitabl ...
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