Post Doctoral Fellowships
Christopher Rankin, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS, NIH)
"Embryonic Stem Cells in the Study of Rett Syndrome Neuropathology"
Mentor: Ronald McKay, Ph.D.
2-Year Award: $80,000
Lay Summary Report:
Rett Syndrome is a neurodevelopmental disorder characterized by progressive cognitive impairment and ataxia. This disease is caused by mutations in the X-linked gene, methyl-CpG-binding protein (MeCP2). The mechanisms leading to neurological dysfunction in Rett Syndrome patients are not well understood.
Pluripotent embryonic stem (ES) cells isolated from the mouse blastula give rise to all differentiated cell types within the mouse and are amenable to genetic manipulations, such as transgene insertion and targeted gene knockouts. In this laboratory, a system has been developed to direct the stepwise differentiation of ES cells first into neural precursors and then into functional neurons and glia. The initial goal of this proposal was to evaluate this system as a model for Rett Syndrome through the use of ES cell lines which carry a mutation in the MeCP2 gene (kindly provided by Dr. Adrian Bird, University of Edinburgh).
Initial experiments using ES cells that carry a mutation in the MeCP2 gene demonstrate that MeCP2 is not required in the formation of neural progenitors, neurons or glia in our system. In addition, MeCP2 mutant ES cells are able to form synapses and differentiate into dopaminergic and serotonergic neurons. Future experiments will focus on examining other aspects of neuronal differentiation, such as neural morphology and electrophysiological responses.
Christopher Rankin, Ph.D.National Institute of Neurological Disorders and Stroke (NINDS, NIH)
"Embryonic Stem Cells in the Study of Rett Syndrome Neuropathology"
Mentor: Ronald McKay, Ph.D.
2-Year Award: $80,000
Lay Summary Report:
Rett Syndrome is a neurodevelopmental disorder characterized by progressive cognitive impairment and ataxia. This disease is caused by mutations in the X-linked gene, methyl-CpG-binding protein (MeCP2). The mechanisms leading to neurological dysfunction in Rett Syndrome patients are not well understood.
Pluripotent embryonic stem (ES) cells isolated from the mouse blastula give rise to all differentiated cell types within the mouse and are amenable to genetic manipulations, such as transgene insertion and targeted gene knockouts. In this laboratory, a system has been developed to direct the stepwise differentiation of ES cells first into neural precursors and then into functional neurons and glia. The initial goal of this proposal was to evaluate this system as a model for Rett Syndrome through the use of ES cell lines which carry a mutation in the MeCP2 gene (kindly provided by Dr. Adrian Bird, University of Edinburgh).
Initial experiments using ES cells that carry a mutation in the MeCP2 gene demonstrate that MeCP2 is not required in the formation of neural progenitors, neurons or glia in our system. In addition, MeCP2 mutant ES cells are able to form synapses and differentiate into dopaminergic and serotonergic neurons. Future experiments will focus on examining other aspects of neuronal differentiation, such as neural morphology and electrophysiological responses.