MECP2e1 Mutation Reduces the Dendritic Complexity of Rett Syndrome Patient iPS Cell-derived Neurons
Year: 2014
Type: dissertation
Abstract: The gene MECP2 that is commonly mutated in Rett Syndrome (RTT) can be alternatively spliced in neurons into MeCP2e1 and MECP2e2 isoforms. Fibroblasts from a patient with a MECP2e1 mutation were reprogrammed into induced pluripotent stem cells (iPS) and differentiated into neurons with an EB-based directed differentiation protocol. I employed methods to analyze neuronal complexity with respect to numbers of terminal dendrites, higher order dendrites, intersections by Sholl analysis, and total dendrite length in RTTe1 compared to wildtype neurons. My results show that neuronal complexity is reduced in the RTTe1 neurons, indicating that the MECP2e1 isoform is essential for healthy neuronal morphology. Wildtype and RTT iPS cells from a MECP2 null and R306C patient were also differentiated into neurons with a one-step protocol by exogenous expression of Ngn2 in iPS cells. RTT neurons did not recapitulate dendritic defects, suggesting that these phenotypes may be masked by Ngn2 overexpression.
Source: TSpace (University of Toronto)
Author: Wesley Lai
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2625534932