Molecular logic of cellular diversification in the mouse cerebral cortex

Nature, Journal Year: 2021, Volume and Issue: 595(7868), P. 554 - 559

Published: June 23, 2021

Language: Английский

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A human tissue screen identifies a regulator of ER secretion as a brain-size determinant

Science, Journal Year: 2020, Volume and Issue: 370(6519), P. 935 - 941

Published: Oct. 29, 2020

Functional screen for microcephaly genes Genetic screens are widely used to identify regulators in biological processes. Human currently limited two-dimensional cell cultures, which lack the ability score tissue-dependent gene function. Esk et al. combined CRISPR-Cas9 screening with barcoded cellular lineage tracing enable loss-of-function three-dimensional human cerebral organoid tissue. By testing candidate genes, endoplasmic reticulum was found control extracellular matrix protein secretion regulating tissue integrity and brain size. This genetic implicates multiple pathways provides a tool systematic of organoids. Science , this issue p. 935

Language: Английский

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Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(3), P. 285 - 294

Published: Feb. 24, 2022

Abstract The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds molecularly diverse cell types in the nervous system, but lineage relationships between mature and are not well understood. Here we show vivo barcoding early progenitors to simultaneously profile phenotypes clonal relations mouse using single-cell spatial transcriptomics. By reconstructing thousands clones, discovered fate-restricted hippocampal neuroepithelium microglia derived few primitive myeloid precursors massively expand generate widely dispersed progeny. We combined with disentangled migration patterns clonally related densely labeled tissue sections. Our approach enables high-throughput dense reconstruction at level individual animals provides an integrated for understanding architecture.

Language: Английский

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Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 11, 2022

Abstract Neuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients 18,969 controls from the ENIGMA consortium, observed that patterns followed normative connectome organization were anchored to prefrontal temporal disease epicenters. Manifold learning revealed frontal-to-temporal sensory/limbic-to-occipitoparietal gradients, differentiating shared illness effects on thickness along these axes. The principal gradient aligned with covariance established transcriptomic link cortico-cerebello-thalamic circuits. Moreover, gradients segregated functional involved basic sensory, attentional/perceptual, domain-general cognitive processes, distinguished between regional cytoarchitectonic profiles. Together, our findings indicate occur synchronized fashion multiple levels of hierarchical organization.

Language: Английский

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Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex

Neuron, Journal Year: 2024, Volume and Issue: 112(13), P. 2091 - 2111

Published: May 15, 2024

Language: Английский

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The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 78(6), P. 2517 - 2563

Published: Dec. 2, 2020

Abstract Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum (ASD), are a large group of in which early insults during brain development result wide heterogeneous clinical diagnoses. Mutations genes coding for chromatin remodelers overrepresented NDD cohorts, pointing towards epigenetics as convergent pathogenic pathway between these disorders. In this review we detail the role NDD-associated developmental continuum progenitor expansion, differentiation, cell-type specification, migration maturation. We discuss how defects remodelling time points compound over impaired circuit establishment. particular, focus on their three largest cell populations: glutamatergic neurons, GABAergic glia cells. An in-depth understanding spatiotemporal neurodevelopment can contribute to identification molecular targets treatment strategies.

Language: Английский

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Genetic mosaicism in the human brain: from lineage tracing to neuropsychiatric disorders

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(5), P. 275 - 286

Published: March 23, 2022

Language: Английский

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Cerebral organoids display dynamic clonal growth and tunable tissue replenishment

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(5), P. 710 - 718

Published: May 1, 2024

During brain development, neural progenitors expand through symmetric divisions before giving rise to differentiating cell types via asymmetric divisions. Transition between those modes varies among individual stem cells, resulting in clones of different sizes. Imaging-based lineage tracing allows for analysis at high cellular resolution but systematic approaches analyse clonal behaviour entire tissues are currently lacking. Here we implement whole-tissue by genomic DNA barcoding 3D human cerebral organoids, show that produce progeny on a vastly variable scale. By using stochastic modelling find sizes arise because subpopulation lineages retains symmetrically dividing cells. We can adjust tissue demands after growth perturbation chemical ablation or genetic restriction subset cells chimeric organoids. Our data suggest adaptive plasticity populations ensures robustness development

Language: Английский

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The regulation of cortical neurogenesis

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2020, Volume and Issue: unknown, P. 1 - 66

Published: Dec. 26, 2020

Language: Английский

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Neurogenesis and Specification of Retinal Ganglion Cells

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(2), P. 451 - 451

Published: Jan. 10, 2020

Across all species, retinal ganglion cells (RGCs) are the first neurons generated during development, followed by other cell types. How progenitor (RPCs) able to produce these types in a specific and timely order? Here, we will review different models of neurogenesis proposed over last decades as well extrinsic intrinsic factors controlling it. We then focus on molecular mechanisms, especially cascade transcription that regulate, more specifically, RGC fate. also comment recent discovery ciliary marginal zone is new stem niche mice contributing neurogenesis, generation ipsilateral RGCs. Furthermore, RGCs composed many subtypes anatomically, physiologically, functionally, molecularly defined. summarize classifications recapitulate specification some them describe how genetic disease such albinism affects resulting profound visual deficits.

Language: Английский

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