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Identifying the role of DNMT1 in gene expression regulation in somatostatinergic interneurons during embryonic corticogenesis [RNA-Seq]

ABSTRACT: The establishment of neuronal circuits, made up of excitatory neurons and inhibitory interneurons, is a fine-tuned process during corticogenesis and is pivotal for a functional brain. Developmental aberrations affecting these circuits are implicated in several neuropsychiatric disorders. While excitatory neurons originate in cortical proliferative zones, inhibitory interneurons migrate from the basal telencephalon into the cortex. This migration is regulated by intrinsic genetic programs and extrinsic cues. Here, we aimed to identify the role of the DNA methyltransferase 1 (DNMT1) in controlling the expression of key genes implicated in mouse cortical interneuron development and the migration of somatostatin-expressing interneurons within the developing cortex.

ORGANISM(S): Mus musculus

PROVIDER: GSE276516 | GEO | 2025/06/18

REPOSITORIES: GEO

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Identifying the role of DNMT1 on methylation signatures in somatostatinergic interneurons during embryonic corticogenesis [EM-seq]

Project description:The establishment of neuronal circuits, made up of excitatory neurons and inhibitory interneurons, is an intricately regulated process during development and is vital for proper brain function. Its perturbations are increasingly implicated in several neuropsychiatric disorders. While excitatory neurons are born in proliferative zones of the cortex, cortical inhibitory interneurons are born in the basal telencephalon and migrate into the cortex. This process is regulated by intrinsic genetic programs as well as extrinsic cues. Here, we aimed to characterize the role of the DNA methyltransferase 1 (DNMT1) in controlling the methylation of key genes implicated in the development and the migration of somatostatin-expressing interneurons within the developing murine cortex.

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Dissecting the cell autonomous and non-autonomous effects of DNMT1 deletion in cortical somatostatinergic interneurons

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Individual Human Cortical Progenitors Can Produce Excitatory and Inhibitory Neurons

Project description:The cerebral cortex is a cellularly-complex structure comprised of a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes—glutamatergic excitatory neurons and GABAergic inhibitory interneurons. Previous developmental studies in rodents have led to the prevailing model that while excitatory neurons are born from progenitors located in the cortex, cortical interneurons are born from a separate population of progenitors located outside of the developing cortex in the ganglionic eminences1-5. However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called “ScRNAseq-compatible Tracer for Identifying Clonal Relationships” (STICR), we were able to perform clonal lineage tracing of 1912 primary human cortical progenitors from six specimens and capture both the transcriptional identities and clonal relationships of their resulting progeny. A subpopulation of cortically-born GABAergic neurons were transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence and these cells were frequently related to excitatory neurons and glia. Thus, our results demonstrate that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex.

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2017-12-01 | GSE93295 | GEO

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Project description:Brain postnatal development is characterized by critical periods of experience dependent remodeling. Maturation of local circuits inhibitory neurons terminate this period of enhanced plasticity. Astroglial cells are known to influence excitatory and inhibitory synaptic transmission as well as network activity through active signaling mechanisms. Although these can be developmentally regulated, the role of astrocytes in the timing of post-natal critical period is unknown. Here we show in the visual cortex that astrocytes con-trol the maturation of inhibitory neurons and thereby closure of the critical period. We uncover a novel underlying pathway involving regulation of the extracellular matrix that allows interneurons maturation via astroglial connexin signaling. We find that timing of the critical period closure is controlled by a marked upregulation of the astroglial protein connexin 30 that inhibits expression of the matrix degrading enzyme MMP9 through the RhoA-GTPase pathway. Our results thus demonstrate that astrocytes not only influ-ence neuronal activity but are also key elements in the experience–dependent wiring of brain circuits. Therefore, astrocytes represent a new cellular partner to consider in our understanding of the post-natal shaping of neuronal activities, hence providing a new target to alleviate malfunctions associated to im-paired closure of the critical period and settling of synaptic circuits.

2022-05-12 | PXD020448 | Pride

Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior [snRNA-Seq]

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2024-11-01 | GSE270237 | GEO

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2018-02-14 | PXD006397 | Pride

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