![]() En1 and Wnt signaling in midbrain dopaminergic neuronal development. Pa圆 transcription factor is required for the interkinetic nuclear movement of neuroepithelial cells. A single-cell molecular map of mouse gastrulation and early organogenesis. Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. ![]() Pa圆 is a human neuroectoderm cell fate determinant. Location of transient ectodermal progenitor potential in mouse development. Foxa2 regulates polarity and epithelialization in the endoderm germ layer of the mouse embryo. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. in Patterning and Cell Type Specification in the Developing CNS and PNS (eds. The single-cell transcriptional landscape of mammalian organogenesis. Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Molecular architecture of the mouse nervous system. A single-cell transcriptional atlas of the developing murine cerebellum. Molecular diversity of midbrain development in mouse, human, and stem cells. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Molecular identity of human outer radial glia during cortical development. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system.Ĭamp, J. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. Previous studies have explored development in specific brain regions 1, 2, 3, 4, 5, 6, 7, 8, the whole adult brain 9 and even entire embryos 10. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. Our results suggest that the BROPA method can produce a preparation suitable for the reconstruction of neural circuits spanning an entire mouse brain.The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell–cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. Using serial block-face electron microscopy (SBEM), we tested human annotator ability to follow neural ‘wires’ reliably and over long distances as well as the ability to detect synaptic contacts. Here we describe a preparation, BROPA (brain-wide reduced-osmium staining with pyrogallol-mediated amplification), that results in the preservation and staining of ultrastructural details throughout the brain at a resolution necessary for tracing neuronal processes and identifying synaptic contacts between them. However, these reconstructions require the undivided brain to be prepared for electron microscopic observation. Because almost all behaviors rely on neural computations widely distributed throughout the brain, a reconstruction of brain-wide circuits-and, ultimately, the entire brain-is highly desirable. Currently only electron microscopy provides the resolution necessary to reconstruct neuronal circuits completely and with single-synapse resolution.
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