Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum

Zhang, Tingting; Liu, Tengyuan; Mora, Natalia; Guégan, Justine; Bertrand, Mathilde; Contreras, Ximena; Hansen, Andi H.; Streicher, Carmen; Anderle, Marica; Danda, Natasha; Tiberi, Luca; Hippenmeyer, Simon; Hassan, Bassem A.

doi:10.1016/j.celrep.2021.109208

Cited by 24 publications

(21 citation statements)

References 79 publications

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“…3, A to C; and fig. S11, A to C), in accord with previous reports ( 34 ). We additionally identified a Gsx1 + population that we traced to the anterior ventricular zone (fig.…”

Section: Progenitor Heterogeneity Reflects Cell Fate Decisionssupporting

confidence: 92%

Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

Sarropoulos

Sepp

Frömel

et al. 2021

Science

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Organ development is orchestrated by cell- and time-specific gene regulatory networks. In this study, we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring snATAC-seq profiles for ~90,000 cells spanning eleven stages, we mapped cerebellar cell types and identified candidate cis-regulatory elements (CREs). We detected extensive spatiotemporal heterogeneity among progenitor cells and a gradual divergence in the regulatory programs of cerebellar neurons during differentiation. Comparisons to vertebrate genomes and snATAC-seq profiles for ∼20,000 cerebellar cells from the marsupial opossum revealed a shared decrease in CRE conservation during development and differentiation, but also differences in constraint between cell types. Our work delineates the developmental and evolutionary dynamics of gene regulation in cerebellar cells and provides insights into mammalian organ development.

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“…3, A to C; and fig. S11, A to C), in accord with previous reports ( 34 ). We additionally identified a Gsx1 + population that we traced to the anterior ventricular zone (fig.…”

Section: Progenitor Heterogeneity Reflects Cell Fate Decisionssupporting

confidence: 92%

Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

Sarropoulos

Sepp

Frömel

et al. 2021

Science

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“…This same bias was first reported by Cepko and colleagues (Jadhav et al, 2006), and they proposed a model in which low levels of Notch promote photoreceptor development, while intermediate levels of Notch signaling causes the MPCs to generate other types of retinal neurons (e.g., ACs and HCs). Recent evidence has shown that like the MPCs of retina, cerebellar progenitors give rise to both inhibitory and excitatory lineages, and the level of Notch signaling determines the fate: cells with low levels of Notch signaling adopt the excitatory fate, while cells with intermediate levels of Notch activity develop as inhibitory neurons (Zhang et al, 2021). Although the mechanism by which this occurs is not understood, the differences we observe in chromatin accessibility near the PTF1A gene suggest that the failure to engage these sites after complete Notch inhibition may in part underlie this difference.…”

Section: Discussionmentioning

confidence: 99%

Single-cell ATAC-seq of fetal human retina and stem-cell-derived retinal organoids shows changing chromatin landscapes during cell fate acquisition

et al. 2022

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“…2c). Finally, GM11, which included genes encoding Notch signalling ligands ( Dll1 , Dll3 ) and effectors ( Hes6 ) promoting neurogenesis 26, 27 , was upregulated in committed enteric neuronal precursors emerging at different stages of mouse and human development (Fig. 2a; Extended Data Fig.…”

Section: Resultsmentioning

confidence: 99%

A branching model of cell fate decisions in the enteric nervous system

Laddach

Chng

Lasrado

et al. 2022

Preprint

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How neurogenesis and gliogenesis are coordinated during development and why mature glial cells often share properties with neuroectodermal progenitors remains unclear. Here, we have used single cell RNA sequencing to map the regulatory landscape of neuronal and glial differentiation in the mammalian enteric nervous system (ENS). Our analysis indicates that neurogenic trajectories branch directly from a linear gliogenic axis defined by autonomic neural crest cells adopting sequential states as they progressively lose their strong neurogenic bias and acquire properties of adult enteric glia. We identify gene modules associated with transcriptional programs driving enteric neurogenesis and cell state transitions along the gliogenic axis. By comparing the chromatin accessibility profile of autonomic neural crest and adult enteric glia we provide evidence that the latter maintain an epigenetic memory of their neurogenic past. Finally, we demonstrate that adult enteric glia maintain neurogenic potential and are capable of generating enteric neurons in certain contexts by activating transcriptional programs employed by early ENS progenitors. Our studies uncover a novel configuration of enteric neurogenesis and gliogenesis that enables the coordinate development of ENS lineages and provides a mechanistic explanation for the ability of enteric glia to be functionally integrated into the adult intestine and simultaneously maintain attributes of early ENS progenitors.

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Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum

Abstract: Highlights d GABAergic and glutamatergic cerebellar neurons are generated from Sox2 + progenitors d Single Sox2 + ECPs can give rise to both excitatory and inhibitory cerebellar neurons d Notch activity mediates GABAergic versus glutamatergic cell fates in Sox2 + ECPs

Cited by 24 publications

References 79 publications

Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

Single-cell ATAC-seq of fetal human retina and stem-cell-derived retinal organoids shows changing chromatin landscapes during cell fate acquisition

A branching model of cell fate decisions in the enteric nervous system

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