Project description:The stress-responsive kinase MKK7 controls various brain functions. Neural stem cell-specific deletion of the Mkk7 gene caused abnormal brain development and death immediately after birth (perinatal lethality). However, the region-specific roles of MKK7 during embryonic brain development remain unclear. We have found that the mice with loss of MKK7 in the cerebrum were born at the expected Mendelian ratio but died within five weeks of birth. To investigate its molecular mechanism, we performed RNA-sequencing analysis in the brain.
Project description:Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and glia. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
Project description:Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and glia. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
Project description:Survey of gene expression in ten common inbred strains of laboratory mouse. Seven brain regions examined: amygdala, basal ganglia, cerebellum, frontal cortex, hippocampus, cingulate cortex, olfactory bulb. Keywords: Genetic background and brain region Sample data tables were removed because the ID_REF identifiers did not match the platform IDs