Project description:Primary cilia act as antennas in cell-cell signalling and are crucial for nervous system development. We explored their role in the development of the murine cerebral cortex using mice mutant for the ciliary gene Inpp5e. We investigated the transcription profile of control and Inpp5e loss-of-function mutants in the E12.5 dorsal telencephalon.
Project description:NeuroD2 targets were identified from embryonic day 14.5 cerebral cortex tissue. The cerebral cortex (dorsal telencelphalon) from E14.5 mouse embryos was dissected and ChIP-SEQ was performed using three separate antibodies against NeuroD2.
Project description:Understanding the pathological basis of the neurological symptoms observed following SARS-CoV2 infection is essential to optimizing outcomes and developing therapeutics. To date, small sample sizes and narrow molecular profiling limit the generalizability of findings. We profiled multiple cortical and subcortical regions in postmortem COVID-19 patient brains and controls (total n=42) with spatial transcriptomics in the frontal cortex, midbrain and pons, bulk RNA expression in frontal cortex, midbrain, basal ganglia, and pons, and proteomics in the 8 regions (frontal cortex, temporal cortex, occipital cortex, midbrain, pons, hippocampus, thalamus and basal ganglia). We observed a multi-regional antiviral response in the absence of direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and up-regulation of neuroinflammation in glia, in both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in various age-related neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging. The data prresented here is a part of the bulk tissue direct gene expression study.
Project description:Understanding the pathological basis of the neurological symptoms observed following SARS-CoV2 infection is essential to optimizing outcomes and developing therapeutics. To date, small sample sizes and narrow molecular profiling limit the generalizability of findings. We profiled multiple cortical and subcortical regions in postmortem COVID-19 patient brains and controls (total n=42) with spatial transcriptomics in the frontal cortex, midbrain and pons, bulk RNA expression in frontal cortex, midbrain, basal ganglia, and pons, and proteomics in the 8 regions (frontal cortex, temporal cortex, occipital cortex, midbrain, pons, hippocampus, thalamus and basal ganglia). We observed a multi-regional antiviral response in the absence of direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and up-regulation of neuroinflammation in glia, in both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in various age-related neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging. The data represented here is a part of the bulk tissue direct gene expression study.
Project description:the goal of the study was to compare gene expression between control and Pbx1; Emx1-cre mutant corteces at e15.5 E15.5 whole cortex was dissected for the analysis. Control embryo genotype was Pbx1F/+. Mutant embryo genotype was Pbx1F/-; Emx1-cre. 4 corteces of each genotype were used for the analysis: 4 controls and 4 mutants, 8 samples total.
Project description:the goal of the study was to compare gene expression between control and Pbx1; Emx1-cre mutant corteces at e12.5 E12.5 whole cortex was dissected for the analysis. Control embryo genotype was Pbx1F/+. Mutant embryo genotype was Pbx1F/-; Emx1-cre. 4 corteces of each genotype were used for the analysis: 4 controls and 4 mutants, 8 samples total.
Project description:We report that miR3607 controls the embryonic cerebral cortex development by regulating neurogenesis, neuron migration and axon growth in a bCatenin signaling pathway dependent manner.