Dr. Fishell is studying directed differentiation of ES cells related to cortical interneuron identities towards neuronal replacement strategies. The strategy is two fold, beginning with established ES cell where the EGFP reporter is under the control of the Dix5/6 locus. This locus is activated broadly in Gabergic populations, including cortical interneurons. The lab complements this by engineering the expression of transcription factors required for cortical interneuron development in ES cell lines and uses extrinsic factors known to function in the specification of cortical interneuron precursors, such as FGF8 and Shh. Validation of method is accomplished through a complementary in vitro/in vivo strategy. The in vitro strategy makes use of cortical interneuron feeder layers, previously shown to allow cortical interneuron precursors to attain their mature characteristics. In vivo transplantation methods are used to reintroduce engineered "cortical interneurons" to ascertain ability to integrate into a functional nervous system.
Gleiberman, A.S., Michurina R., Encinas, J.M., Roig, J.L., Krasnov, P., Balordi, F., Fishell, G., Rosenfeld, M.G., Enikolopov, G. (2008). Genetic approaches identify adult pituitary stem cells. PNAS 2008; 105:6332-6337.
Balordi, F., Fishell, G. (2007). Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal. J Neurosci. 2007; 27:14248-14259.
Balordi, F., Fishell, G. (2007). Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci. 2007; 27: 5936-5947.