Cux1 and Cux2 regulate dendritic branching, spine morphology, and synapses of the upper layer neurons of the cortex. DMRTA2 ( DMRT5) is mutated in a novel cortical brain malformation. Chromatin potential identified by shared single-cell profiling of RNA and chromatin. Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation. Perturb-seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. DeCoN: genome-wide analysis of in vivo transcriptional dynamics during pyramidal neuron fate selection in neocortex. A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain. A translational repression complex in developing mammalian neural stem cells that regulates neuronal specification. Fate-restricted neural progenitors in the mammalian cerebral cortex. Deterministic progenitor behavior and unitary production of neurons in the neocortex. Fezf2 expression identifies a multipotent progenitor for neocortical projection neurons, astrocytes, and oligodendrocytes. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. Radial glia – from boring cables to stem cell stars. Hes6 inhibits astrocyte differentiation and promotes neurogenesis through different mechanisms. Neural progenitors, neurogenesis and the evolution of the neocortex. Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis. (Allen Institute for Brain Science, 2015).įarrell, J. Shared and distinct transcriptomic cell types across neocortical areas. Three types of cortical layer 5 neurons that differ in brain-wide connectivity and function. Deep learning and alignment of spatially-resolved whole transcriptomes of single cells in the mouse brain with Tangram. Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2. Multiple origins of Cajal–Retzius cells at the borders of the developing pallium. Developmental diversification of cortical inhibitory interneurons. Transcriptomic and anatomic parcellation of 5-HT 3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing. Developmental emergence of adult neural stem cells as revealed by single-cell transcriptional profiling. Molecular logic of neocortical projection neuron specification, development and diversity. Generating neuronal diversity in the mammalian cerebral cortex. The data provide a global picture of the regulatory mechanisms that govern cellular diversification in the neocortex. Finally, we demonstrate how this developmental map pinpoints the origin of lineage-specific developmental abnormalities that are linked to aberrant corticogenesis in mutant mice. We computationally reconstruct developmental trajectories across the diversity of cortical cell classes, and infer their spatial organization and the gene regulatory programs that accompany their lineage bifurcation decisions and differentiation trajectories. We sampled the neocortex every day throughout embryonic corticogenesis and at early postnatal ages, and complemented the sequencing data with a spatial transcriptomics time course. Here we generate a comprehensive atlas of the developing mouse neocortex, using single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing. However, the molecular logic that governs the establishment and organization of cortical cell types remains unknown, largely due to the large number of cell classes that undergo dynamic cell-state transitions over extended developmental timelines. The mammalian cerebral cortex has an unparalleled diversity of cell types, which are generated during development through a series of temporally orchestrated events that are under tight evolutionary constraint and are critical for proper cortical assembly and function 1, 2.
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