The Effect of Mecp2 Mutation on Cortical Projections Revealed by Correlated Single-Cell Transcriptomics and Projectomics
Technical Report,01 Apr 2019,31 Mar 2020
Cold Spring Harbor Laboratory Cold Spring Harbor United States
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Rett Syndrome is caused by mutations in Mecp2, which result in a constellation of language, cognitive, motor, and autonomic deficits later in life. Although changes in long-range neuronal connectivity likely underlie the behavioral defects in Rett syndrome, it is unclear how long-range axonal projections are disrupted. Here we develop and apply high-throughput single-cell techniques to identify cell type-specific changes in projections in Mecp2 animals. Initial analysis indicates that corticothalamic neurons are reduced in both the visual cortex and anterior cingulate cortex in Mecp2 animals. This result is the first step in identifying the long-range circuitry changes associated with Mecp2 mutation. Furthermore, our approach is generally applicable to other brain areas and disease models to reveal cell type-specific changes in projections that are difficult to detect using conventional methods.
- Medicine and Medical Research