Developmental emergence of cortical neurogliaform cell diversity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA936871 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:GABAergic interneurons are key regulators of cortical circuit function. Among the dozens of reported transcriptionally distinct subtypes of cortical interneurons, neurogliaform cells (NGC) are unique: are recruited by long-range excitatory inputs and the primary source of slow cortical inhibition. Despite their functional importance, the developmental emergence and cellular diversity of NGCs remains unclear. Here, combining single-cell transcriptomics, genetic fate-mapping, electrophysiological morphological characterization, we reveal that discrete molecular subtypes of NGCs, with distinctive functional and anatomic profiles, populate the neocortex. Furthermore, we show that NGC subtypes emerge gradually through development, as incipient differential molecular signatures are apparent in Preoptic Area (POA) born NGC precursors. By identifying NGC developmentally-conserved transcriptional programs, we report that the transcription factor Tox2 constitutes an identity hallmark across NGC subtypes. Using CRISPR-Cas9-mediated genetic loss-of-function, we show that Tox2 is critical for NGC development: POA-born cells lacking Tox2 fail to differentiate into NGCs. Together, these results reveal that NGCs are born from a spatially restricted pool of Tox2+ POA precursors, after which intra-type diverging molecular programs are gradually acquired post-mitotically and result in functionally and molecularly discrete NGC cortical subtypes.
2023-06-30 | GSE225639 | GEO
Project description:GABAergic interneurons play crucial roles in the regulation of neural circuit activity in the cerebral cortex. A hallmark of cortical interneurons is their remarkable structural and functional diversity, yet the molecular determinants and the precise timing underlying their diversification remain largely unknown. Here we use single-cell transcriptomics to identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors define temporally and spatially restricted transcriptional trajectories that unambiguously relate to specific classes of interneurons in the adult cerebral cortex. Our findings therefore suggest that interneuron diversity is already patent shortly after neurons become postmitotic through the acquisition of specific transcriptional programs that unfold over several weeks in the developing cortex
2018-03-06 | GSE109796 | GEO
Project description:Early emergence of cortical interneuron diversity in the mouse embryo
| PRJNA432054 | ENA
Project description:GABAergic interneurons are key regulators of cortical circuit function. Among the dozens of reported transcriptionally distinct subtypes of cortical interneurons, neurogliaform cells (NGCs) are unique: they are recruited by long-range excitatory inputs, are a source of slow cortical inhibition and are able to modulate the activity of large neuronal populations. Despite their functional relevance, the developmental emergence and diversity of NGCs remains unclear. Here, by combining single-cell transcriptomics, genetic fate mapping, and electrophysiological and morphological characterization, we reveal that discrete molecular subtypes of NGCs, with distinctive anatomical and molecular profiles, populate the mouse neocortex. Furthermore, we show that NGC subtypes emerge gradually through development, as incipient discriminant molecular signatures are apparent in preoptic area (POA)-born NGC precursors. By identifying NGC developmentally conserved transcriptional programs, we report that the transcription factor Tox2 constitutes an identity hallmark across NGC subtypes. Using CRISPR-Cas9-mediated genetic loss of function, we show that Tox2 is essential for NGC development: POA-born cells lacking Tox2 fail to differentiate into NGCs. Together, these results reveal that NGCs are born from a spatially restricted pool of Tox2+ POA precursors, after which intra-type diverging molecular programs are gradually acquired post-mitotically and result in functionally and molecularly discrete NGC cortical subtypes.
| S-EPMC10445751 | biostudies-literature
Project description:The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge through the implementation of different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons, as they represent a relatively small proportion of all cortical cells, migrate tangentially from their embryonic origin to the cerebral cortex, and have a protracted development. Here we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells, the most diverse subclass of inhibitory neurons in the mouse cerebral cortex. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is further refined during early postanal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons. Thus, the diversification of SST+ inhibitory neurons involves a temporal cascade of unique molecular programs driving their divergent developmental trajectories.
2023-11-01 | GSE217065 | GEO
Project description:Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.
2021-07-01 | GSE116944 | GEO
Project description:Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.
2021-07-01 | GSE118681 | GEO
Project description:Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.
2021-07-01 | GSE156080 | GEO
Project description:Adult neural stem cells (NSCs) derive from embryonic precursors, but little is known about how or when this occurs. We have addressed this issue using single cell RNAseq at multiple developmental timepoints to analyze the embryonic murine cortex, one source of adult forebrain NSCs. We computationally identify all major cortical cell types, including the embryonic radial precursors (RPs) that generate adult NSCs. We define the initial emergence of RPs from neuroepithelial stem cells at E11.5. We show that by E13.5 these RPs express a transcriptional identity that is maintained and reinforced throughout their transition to a non-proliferative state between E15.5 and E17.5. These slowly-proliferating late embryonic RPs share a core transcriptional phenotype with quiescent adult forebrain NSCs. Together, these findings support a model where cortical RPs maintain a core transcriptional identity from embryogenesis through to adulthood, and where the transition to a quiescent adult NSC occurs during late neurogenesis.
2017-12-26 | GSE107122 | GEO
Project description:Developmental diversification of cortical inhibitory interneurons
| PRJNA411832 | ENA