Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon
Lachlan H Thompson1, Elin Andersson, Josephine B Jensen
1Wallenberg Neuroscience Center, Department of Experimental Medical Science, and Lund Strategic Center for Stem Cell Biology and Cell Therapy, Lund University, BMC A11, SE-221 84 Lund, Sweden.
Experimental Neurology
|January 28, 2006
Summary
Researchers identified Neurogenin2 (Ngn2) as a key marker for isolating mesencephalic dopamine (mesDA) neuron precursors. This discovery enables the selective isolation of transplantable mesDA neuron precursors for neural transplantation therapies.
Area of Science:
- Neuroscience
- Developmental Biology
- Stem Cell Research
Background:
- Identifying specific neural precursors is crucial for successful neural transplantation.
- Mesencephalic dopamine (mesDA) neurons are critical for motor control and are lost in Parkinson's disease.
- The proneural gene Neurogenin2 (Ngn2) is known to be involved in mesDA neuron development.
Purpose of the Study:
- To identify and isolate mesencephalic dopamine (mesDA) neuron precursors for transplantation.
- To determine if Ngn2 expression can be used to distinguish mesDA neuron precursors from other cell types.
- To evaluate the potential of Ngn2-expressing cells for generating functional mesDA neurons in vitro and in vivo.
Main Methods:
- Utilized Ngn2-GFP knock-in mice to track Ngn2 expression in the developing ventral mesencephalon (VM).
- Employed fluorescence-activated cell sorting (FACS) to isolate Ngn2-GFP-expressing and non-expressing cells.
- Assessed the differentiation potential of isolated cells in vitro and after transplantation into neonatal rat striatum.
Main Results:
- Ngn2 is exclusively expressed in VM ventricular zone cells that give rise to mesDA neuroblasts, not in differentiated mesDA neurons.
- FACS-isolated Ngn2-GFP-expressing cells generated mesDA neurons in vitro and after transplantation.
- Ngn2-GFP+ population contained all mesDA neuron precursors but not serotonergic or GABAergic precursors; glial cells derived from Ngn2-GFP-negative fraction.
- Transplanted mesDA neurons originated from early postmitotic, Nurr1-expressing precursors.
Conclusions:
- Ngn2 serves as a reliable marker for identifying and isolating mesDA neuron precursors from the developing VM.
- The Ngn2-GFP reporter system facilitates the selective isolation of transplantable mesDA neuron precursors.
- This approach holds promise for advancing neural transplantation strategies for neurodegenerative diseases affecting dopaminergic systems.
