Journal
NEURON
Volume 81, Issue 1, Pages 103-119Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2013.10.051
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Funding
- National Institutes of Health [P30 CA006973]
- Human Frontier Science Program
- Howard Hughes Medical Institute
- Brain Sciences Institute of the Johns Hopkins University
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Female eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from similar to 4% of the genome. To quantitatively map the topography of XCI for defined cell types at single cell resolution, we have generated female mice that carry X-linked, Cre-activated, and nuclear-localized fluorescent reporters-GFP on one X chromosome and tdTomato on the other. Using these reporters in combination with different Cre drivers, we have defined the topographies of XCI mosaicism for multiple CNS cell types and of retinal vascular dysfunction in a model of Norrie disease. Depending on cell type, fluctuations in the XCI mosaic are observed over a wide range of spatial scales, from neighboring cells to left versus right sides of the body. These data imply a major role for XCI in generating female-specific, genetically directed, stochastic diversity in eutherian mammals on spatial scales that would be predicted to affect CNS function within and between individuals.
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