Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells
2007
Directed differentiation and purification of mesencephalic dopaminergic
(mesDA) neurons from stem cells are crucial issues for realizing safe and
efficient cell transplantation therapies for Parkinson9s disease. Although
recent studies have identified the factors that regulate mesDA neuron
development, the mechanisms underlying mesDA neuron specification are not
fully understood. Recently, it has been suggested that mesencephalic floor
plate (FP) cells acquire neural progenitor characteristics to generate mesDA
neurons. Here, we directly examined this in a fate mapping experiment using
fluorescence-activated cell sorting (FACS) with an FP cell-specific surface
marker, and demonstrate that mesencephalic FP cells have neurogenic activity
and generate mesDA neurons in vitro. By contrast, sorted caudal FP cells have
no neurogenic potential, as previously thought. Analysis of dreher mutant mice
carrying a mutation in the Lmx1a locus and transgenic mice ectopically
expressing Otx2 in caudal FP cells demonstrated that Otx2 determines anterior
identity that confers neurogenic activity to FP cells and specifies a mesDA
fate, at least in part through the induction of Lmx1a. We further show that
FACS can isolate mesDA progenitors, a suitable transplantation material, from
embryonic stem cell-derived neural cells. Our data provide insights into the
mechanisms of specification and generation of mesDA neurons, and illustrate a
useful cell replacement approach for Parkinson9s disease.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
31
References
260
Citations
NaN
KQI