Jordan Straight

Nato3 induces the expression of key DA neuron markers in a regionally and temporally specific manner within the developing CNS

In the developing stages of the central nervous system (CNS), neural stem cells gradually adopt specific cell fates and differentiate accordingly. The floor plate of the developing midbrain gives rise to dopaminergic (DA) neurons, an important class of neurons involved in Parkinson’s disease. Better understanding of the mechanisms by which DA neurons are created is of great interest and would accelerate promising applications such as cell replacement therapies. Nato3, a basic helix-loop-helix transcription factor, is expressed in the floor plate region of the midbrain during development.  In vitro studies suggest that Nato3 overexpression is sufficient to promote floor plate and DA neuron marker expression, whereas in vivo studies suggest that Nato3 is not.  Here, we show that overexpression of Nato3 in the developing chick produces a regionally and temporally dependent increase in DA neuron markers Nurr1 (an immature DA neuron marker) and tyrosine hydroxylase (TH) (a mature DA neuron marker) within the ventral midbrain. In-ovo electroporation was used for transfection, and Nato3 overexpression was monitored using a bicistronic EGFP reporter expression vector. The observed effects were characterized by quantitative PCR and immunohistochemistry. The regionally specific action of Nato3 on DA neuron markers suggests that it is regulated by an unknown mechanism that functions early in development within the ventral midbrain. These data provide new insight into the action of Nato3 on DA neuron marker expression in vivo and help to better characterize the role that Nato3 plays in DA neurogenesis.

Faculty Mentor: Merritt Taylor, Biomedical Science

Page last modified August 2, 2013