Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

Telley, Ludovic; Agirman, Gulistan; Prados, Julien; Amberg, Nicole; Fièvre, Sabine; Oberst, Polina; Bartolini, Giorgia; Vitali, Ilaria; Cadilhac, Christelle; Hippenmeyer, Simon; Nguyen, Laurent; Dayer, Alexandre; Jabaudon, Denis

doi:10.1126/science.aav2522

Cited by 321 publications

(488 citation statements)

References 55 publications

(62 reference statements)

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“…The hypothesis of cellular homology also prescribes that the same cell types were anatomically "rearranged" into distinct laminae in the mammalian neocortex and into distinct components of the sauropsid DVR, by coopting different developmental mechanisms (Briscoe & Ragsdale, 2018a. We strongly agree with this assertion in terms of the mechanisms: In the neocortex, a single neural progenitor from the dorsal pallium sequentially generates the components of the microcircuit (Telley et al, 2019). On the contrary, the microcircuit of the avian DVR is assembled from different neural progenitors located in distinct regions of the lateral-ventral pallium (Suzuki, Kawasaki, Gojobori, & Hirata, 2012).…”

Section: Revived: a Conserved Pallial Microcircuitsupporting

confidence: 56%

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes

Aboitiz

Montiel

2019

Evolution and Development

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Although the cerebral hemispheres are among the defining characters of vertebrates, each vertebrate class is characterized by a different anatomical organization of this structure, which has become highly problematic for comparative neurobiology. In this article, we discuss some mechanisms involved in the generation of this morphological divergence, based on simple spatial constraints for neurogenesis and mechanical forces generated by increasing neuronal numbers during development, and the different cellular strategies used by each group to overcome these limitations. We expect this view to contribute to unify the diverging vertebrate brain morphologies into general, simple mechanisms that help to establish homologies across groups. K E Y W O R D Sbasal progenitors, dorsal ventricular ridge, eversion, ganglionic eminences, neocortex, subventricular zone, telencephalon, ventricular zone

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Section: Revived: a Conserved Pallial Microcircuitsupporting

confidence: 56%

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes

Aboitiz

Montiel

2019

Evolution and Development

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“…Single cell sequencing technologies can measure multiple molecular signatures of cell identity. The core molecular identity of a cell is largely established during development and maintained by a combination of gene regulatory proteins, such as transcription factors, and epigenetic marks, such as open chromatin and DNA methylation 6,7 . The expression of specific cell fate-determining proteins promotes stable, covalent modifications of chromatin and DNA, while epigenetic marks in turn shape and maintain cell type-specific gene expression.…”

Section: Introductionmentioning

confidence: 99%

An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types

Yao

Liu

Xie

et al. 2020

Preprint

138

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Single cell transcriptomics has transformed the characterization of brain cell identity by providing quantitative molecular signatures for large, unbiased samples of brain cell populations. With the proliferation of taxonomies based on individual datasets, a major challenge is to integrate and validate results toward defining biologically meaningful cell types. We used a battery of single-cell transcriptome and epigenome measurements generated by the BRAIN Initiative Cell Census Network (BICCN) to comprehensively assess the molecular signatures of cell types in the mouse primary motor cortex (MOp). We further developed computational and statistical methods to integrate these multimodal data and quantitatively validate the reproducibility of the cell types. The reference atlas, based on more than 600,000 high quality single-cell or -nucleus samples assayed by six molecular modalities, is a comprehensive molecular account of the diverse neuronal and non-neuronal cell types in MOp.Collectively, our study indicates that the mouse primary motor cortex contains over 55 neuronal cell types that are highly replicable across analysis methods, sequencing technologies, and modalities. We find many concordant multimodal markers for each cell type, as well as thousands of genes and gene regulatory elements with discrepant transcriptomic and epigenomic signatures. These data highlight the complex molecular regulation of brain cell types and will directly enable design of reagents to target specific MOp cell types for functional analysis. IntroductionNeural circuits are characterized by extraordinary diversity of their cellular components 1,2 . Single-cell molecular assays, especially transcriptomic measurements by RNA-Seq, have accelerated the discovery and characterization of cell types across brain regions and in diverse species. Recent advances include single-cell transcriptome datasets with >10 5 individual cells, identifying hundreds of neuronal and non-neuronal cell types across the mouse nervous system 3-5 . As the number of profiled cells grows into the millions, a key question is whether these data will converge toward a comprehensive and coherent taxonomy of cell types with broad utility for organizing knowledge of brain cells and their function. Data from different modalities, including transcriptomic and epigenomic data, must be cross-referenced and integrated to establish robust and consistent cell type classifications.Although a comprehensive atlas should incorporate anatomical and physiological information, the high throughput of single cell sequencing assays makes integration of molecular data a particularly urgent challenge. A rigorous and reproducible consensus molecular atlas of brain cell types would drive progress across modalities, including obtaining functional information.Single cell sequencing technologies can measure multiple molecular signatures of cell identity. The core molecular identity of a cell is largely established during development and maintained by a combination of gene regulatory proteins...

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“…1i, data not shown). These data show that 6 Shh/Gli signaling is required for sustained expression of Phox2b and Nkx2.9 and suggest that inhibition of Shh signaling is sufficient to trigger a MN-to-5HTN fate switch.…”

Section: Shh/gli Signaling Promotes Expression Of Phox2bmentioning

confidence: 63%

A Shh/Gli-driven three-node timer motif controls temporal identity and fate of neural stem cells

Dias

Alekseenko

Jeggari

et al. 2019

Preprint

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How time is measured by neural stem cells during temporal neurogenesis has remained unresolved. By combining experiments and computational modelling, we here define a Shh/Gli-driven three-node timer underlying the sequential generation of motor neurons (MNs) and serotonergic neurons in the brainstem. The timer is founded on temporal decline of Gliactivator and Gli-repressor activities established through downregulation of Gli transcription.The circuitry conforms an incoherent feedforward loop, whereby Gli proteins promote expression of Phox2b and thereby MN-fate, but also account for a delayed activation of a selfpromoting Tgfβ-node triggering a fate switch by repressing Phox2b. Hysteresis and spatial averaging by diffusion of Tgfβ counteracts noise and increases temporal accuracy at the population level. Our study defines how time is reliably encoded during the sequential specification of neurons. Main textTime is a central axis of information during embryogenesis but few mechanisms explaining the timing of developmental events have been resolved 1-4 . In the forming central nervous system (CNS), defined pools of multipotent neural stem cells (NSCs) produce distinct cell types in a specific sequential order and over defined timeframes. In this process, ageing NSCs become progressively restricted in their developmental potential by losing competence to generate early-born cell types 5 and genome-wide analyses have revealed that NSCs undergo dynamic transcriptional changes over time 6 . However, the composition and functional properties of time-encoding circuitries determining timeframes and point of transitions have not been resolved in any model system 7,8 . Temporal neural patterning in vertebrates is a slow process progressing over days or even weeks depending on species 9,10 . Yet, in several lineages, progenitors undergo remarkably coordinated and fast temporal transitions 9-13 . 3 Biological timers regulating temporal neurogenesis are therefore likely to exhibit properties that counterbalance noise in regulatory networks, but how this is achieved at the molecular level remains unknown.Temporal patterning contributes to the generation of neural cell diversity at all axial levels of the CNS, but only few transcription factors (TFs) and/or signaling molecules regulating temporal fate and potency have been defined in various temporal lineages of the vertebrate CNS 11,12 . To approach the question of time, we focused on a relatively well-defined lineage in the ventral brainstem that sequentially produces motor neurons (MNs), serotonergic neurons (5HTNs) and oligodendrocyte precursors (OPCs) 13,14 . The lineage is induced by Sonic hedgehog (Shh) and defined by the expression of the TF Nkx2.2 13 , and the temporal progression of differentiation is easy to monitor as the NSC-pool remains at a fixed position and does not comprise the specification of proliferative intermediate progenitors as in the developing neocortex 12 . Nkx2.2 + NSCs show otherwise many common features to cortical progenitors, as young NSCs a...

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Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

Cited by 321 publications

References 55 publications

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes

An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types

A Shh/Gli-driven three-node timer motif controls temporal identity and fate of neural stem cells

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