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NGN2-GFP sorted progenitors

In neural transplantation studies there is an interest in identifying and isolating mesencephalic dopamine (mesDA) neuron precursors that have the capacity to differentiate into fully mature mesDA neurons after transplantation. We report here that in the developing ventral mesencephalon (VM) the proneural gene Neurogenin2 (Ngn2) is expressed exclusively in the part of the ventricular zone that gives rise to the migrating mesDA neuroblasts, but not in the differentiated mesDA neurons. Previous studies have demonstrated that Ngn2 is involved in induction of neurogenesis as well as in the specification of progenitor cell identity.

We show that cells isolated by FACS from the developing VM of Ngn2-GFP knock-in mice are capable of generating mesDA neurons, both in vitro and after transplantation to the striatum of neonatal rats. All mesDA neuron precursors, but not the serotonergic or GABAergic neuron precursors, are contained in the Ngn2-GFP-expressing population, indicating that Ngn2 is selectively involved in the generation of mesDA neurons within the developing VM. Furthermore, we report that surviving mesDA neurons in VM grafts are derived from early post-mitotic, probably Nurr1-expressing precursors before they have acquired their fully differentiated neuronal phenotype.

These results open possibilities to use expression of the proneural gene Ngn2 as a marker for an early progenitor of mesencephalic dopamine neurons. Nevertheless, no immediate use or commersial application is envisoned at this stage.

A complete account of the research finding is now in pree in Experimental Neurology.

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