A5019165780- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Neurotransmitter Receptor Influence on Behavior
- DNA Repair Mechanisms
- Psychedelics and Drug Studies
- Tryptophan and brain disorders
University of Michigan
2020-2025
There is growing interest to investigate classic psychedelics as potential therapeutics for mental illnesses. Previous studies have demonstrated that one dose of psilocybin leads persisting neural and behavioral changes. The durability psilocybin's effects suggests there are likely alterations gene expression at the transcriptional level. In this study, we performed single-nucleus RNA sequencing dorsal medial frontal cortex male female mice. Samples were collected 1, 2, 4, 24, or 72 hours...
Abstract Chromatin regulates spatiotemporal gene expression during neurodevelopment, but it also mediates DNA damage repair essential to proliferating neural progenitor cells (NPCs). Here, we uncover molecularly dissociable roles for nucleosome remodeler Ino80 in chromatin-mediated transcriptional regulation and genome maintenance corticogenesis. We find that conditional deletion from cortical NPCs impairs double-strand break (DSB) repair, triggering p53-dependent apoptosis microcephaly....
Histone variants, which can be expressed outside of S-phase and deposited DNA synthesis-independently, provide long-term histone replacement in postmitotic cells, including neurons. Beyond replenishment, variants also play active roles gene regulation by modulating chromatin states or enabling nucleosome turnover. Here, we uncover crucial for the H3 variant H3.3 neuronal development. We find that newborn cortical excitatory neurons, have only just completed replication-coupled deposition...
Significance The cognitive, perceptive, and motor capabilities of the mammalian cerebral cortex depend on assembly circuit connectivity during development. Subplate neurons, strategically located at junction gray white matter, orchestrate wiring cortical circuits. Using a genetic approach to study gene necessity sufficiency in subplate we uncover an essential role for chromatin remodeler Arid1a neuron expression axon guidance functions. Cortical deletion disrupts subplate-dependent formation...
Abstract Histone variants, which can be expressed outside of S-phase and deposited DNA synthesis-independently, provide long-term histone replacement in postmitotic cells, including neurons. Beyond replenishment, variants also play active roles gene regulation by modulating chromatin states or enabling nucleosome turnover. Here, we uncover crucial for the H3 variant H3.3 neuronal development. We find that newborn cortical excitatory neurons, have only just completed replication-coupled...
Abstract Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, developmental disorder characterized by dysgenesis corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for subplate neurons. Subplate neurons (SPNs), strategically positioned at the interface grey white matter, orchestrate multiple processes indispensable neural circuit wiring. We that pan-cortical deletion leads to...