Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression in cortical interneuron precursors is prescient of their mature function.

ABSTRACT: At present little is known about the developmental mechanisms that give rise to inhibitory gamma-aminobutyric acidergic interneurons of the neocortex or the timing of their subtype specification. As such, we performed a gene expression microarray analysis on cortical interneuron precursors isolated through their expression of a Dlx5/6(Cre-IRES-EGFP) transgene. We purified these precursors from the embryonic mouse neocortex at E13.5 and E15.5 by sorting of enhanced green fluorescent protein-expressing cells. We identified novel transcription factors, neuropeptides, and cell surface genes whose expression is highly enriched in embryonic cortical interneuron precursors. Our identification of many of the genes known to be selectively enriched within cortical interneurons validated the efficacy of our approach. Surprisingly, we find that subpopulations of migrating cortical interneurons express genes encoding for proteins characteristic of mature interneuron subtypes as early as E13.5. These results provide support for the idea that many of the genes characteristic of specific cortical interneuron subtypes are evident prior to their functional integration into cortical microcircuitry. They suggest interneurons are already relegated to specific genetic subtypes shortly after they become postmitotic. Moreover, our work has revealed that many of the genes expressed in cortical interneuron precursors have been independently linked to neurological disorders in both mice and humans.

SUBMITTER: Batista-Brito R

PROVIDER: S-EPMC2536702 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Islet1 Precursors Contribute to Mature Interneuron Subtypes in Mouse Neocortex.

Project description:Cortical interneurons (GABAergic cells) arise during embryogenesis primarily from the medial and caudal ganglionic eminences (MGE and CGE, respectively) with a small population generated from the preoptic area (POA). Progenitors from the lateral ganglionic eminence (LGE) are thought to only generate GABAergic medium spiny neurons that populate the striatum and project to the globus pallidus. Here, we report evidence that neuronal precursors that express the LGE-specific transcription factor Islet1 (Isl1) can give rise to a small population of cortical interneurons. Lineage tracing and homozygous deletion of Nkx2.1 in Isl1 fate-mapped mice showed that neighboring MGE/POA-specific Nkx2.1 cells and LGE-specific Isl1 cells make both common and distinct lineal contributions towards cortical interneuron fate. Although the majority of cells had overlapping transcriptional domains between Nkx2.1 and Isl1, a population of Isl1-only derived cells also contributed to the adult cerebral cortex. The data indicate that Isl1-derived cells may originate from both the LGE and the adjacent LGE/MGE boundary regions to generate diverse neuronal progeny. Thus, a small population of neocortical interneurons appear to originate from Isl-1-positive precursors.

| S-EPMC8491676 | biostudies-literature

Prospective isolation of cortical interneuron precursors from mouse embryonic stem cells.

Project description:Despite their therapeutic potential, progress in generating fully differentiated forebrain neurons from embryonic stem cells (ESCs) has lagged behind that from more caudal regions of the neuraxis. GABAergic interneuron precursors have the remarkable ability to migrate extensively and survive after transplantation into postnatal cortex, making them an attractive candidate for use in cell-based therapy for seizures or other neuropsychiatric disorders. We have modified a mouse ESC line with an Lhx6-GFP reporter construct that allows for the isolation of newly generated cortical interneuron precursors. When transplanted into postnatal cortex, these cells can migrate into the cortical parenchyma, survive for months, and display morphological, neurochemical, and electrophysiological properties characteristic of mature interneurons. This work demonstrates that forebrain neuronal subtypes with complex traits can be generated from embryonic stem cells, and provides a novel approach to the study of cortical interneuron development and to the establishment of cell-based therapies for neurological disease.

| S-EPMC2868507 | biostudies-literature

Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice.

Project description:Epilepsy, a disease characterized by abnormal brain activity, is a disabling and potentially life-threatening condition for nearly 1% of the world population. Unfortunately, modulation of brain excitability using available antiepileptic drugs can have serious side effects, especially in the developing brain, and some patients can only be improved by surgical removal of brain regions containing the seizure focus. Here, we show that bilateral transplantation of precursor cells from the embryonic medial ganglionic eminence (MGE) into early postnatal neocortex generates mature GABAergic interneurons in the host brain. In mice receiving MGE cell grafts, GABA-mediated synaptic and extrasynaptic inhibition onto host brain pyramidal neurons is significantly increased. Bilateral MGE cell grafts in epileptic mice lacking a Shaker-like potassium channel (a gene mutated in one form of human epilepsy) resulted in significant reductions in the duration and frequency of spontaneous electrographic seizures. Our findings suggest that MGE-derived interneurons could be used to ameliorate abnormal excitability and possibly act as an effective strategy in the treatment of epilepsy.

| S-EPMC2741275 | biostudies-literature

Sip1 in cortical interneuron migration

Project description:We sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples

2012-12-07 | E-GEOD-35616 | biostudies-arrayexpress

Postmitotic Prox1 Expression Controls the Final Specification of Cortical VIP Interneuron Subtypes.

Project description:Throughout development, neuronal identity is controlled by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 regulates VIP-positive cortical interneuron migration, survival, and connectivity. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early postnatal life. Synaptic in vitro electrophysiology in male and female mice shows that postnatal Prox1 removal differentially affects the dynamics of excitatory inputs onto VIP bipolar and multipolar subtypes. RNA sequencing reveals that one of the downstream targets of Prox1 is the postsynaptic protein Elfn1, a constitutive regulator of presynaptic release probability. Further genetic, pharmacological, and electrophysiological experiments demonstrate that removing Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Finally, overexpression experiments and analysis of native Elfn1 mRNA expression reveal that Elfn1 levels are differentially controlled at the post-transcriptional stage. Thus, in addition to activity-dependent processes that contribute to the developmental trajectory of VIP cells, genetic programs engaged by Prox1 control the final differentiation of multipolar and bipolar subtypes.SIGNIFICANCE STATEMENT The transcription factor Prox1 generates functional diversification of cortical VIP interneuron subtypes in early postnatal life, thus expanding the inhibitory repertoire of the cortex.

| S-EPMC8482865 | biostudies-literature

Assessment of gene expression changes during human cortical interneuron development

Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells (hESCs) to study gene expression changes during this process, to identify regulatory networks critical to cortical interneuron development. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like progenitors), day 35 (immature interneurons), and day 60 (mature interneurons).

2024-04-18 | GSE239396 | GEO

A modular gain-of-function approach to generate cortical interneuron subtypes from ES cells.

Project description:Whereas past work indicates that cortical interneurons (cINs) can be generically produced from stem cells, generating large numbers of specific subtypes of this population has remained elusive. This reflects an information gap in our understanding of the transcriptional programs required for different interneuron subtypes. Here, we have utilized the directed differentiation of stem cells into specific subpopulations of cortical interneurons as a means to identify some of these missing factors. To establish this approach, we utilized two factors known to be required for the generation of cINs, Nkx2-1 and Dlx2. As predicted, their regulated transient expression greatly improved the differentiation efficiency and specificity over baseline. We extended upon this "cIN-primed" model in order to establish a modular system whereby a third transcription factor could be systematically introduced. Using this approach, we identified Lmo3 and Pou3f4 as genes that can augment the differentiation and/or subtype specificity of cINs in vitro.

| S-EPMC5085060 | biostudies-literature

Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice.

Project description:There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months). We first assessed markers of bone turnover in control (non-loaded) mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001). There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001). We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (-1300 µε endocortical; -2350 µε periosteal). Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month) mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001). In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV) than contralateral control tibias (p<0.05), due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages). In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2-12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice.

| S-EPMC3325918 | biostudies-literature

Comparative analysis of different cortical interneuron groups.

Project description:GABAergic interneuron in the cortex comprise a very heterogenous group. and it is critical to identify discrete interneuron types to understand how their contributions to behavior can be modulated by external and internal cues. However, molecular difinition of these interneuron cell groups has been difficult. Comparative analysis of different interneuron subtypes can provide us new candidate marker genes which could target more specific interneu?on cell group. Here we identify oxytocin responsive novel class of interneuron through our comparative analysis. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from Nek7, Dlx1, Cort, Htr3a, Oxtr expressing cortical interneurons. We show that Oxtr expressing cells are a subtype of somatostatin positive interneurons. Three independent TRAP replicates were collected and total RNA from the immunoprecipitates or flow-through (input) whole cortex lysates were amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the Nek7 BAC labels non-neuronal cells, we recommend to delete astrocytes and oligodendrocytes genes from the list using GSE13379 data.

2014-10-07 | E-GEOD-56996 | biostudies-arrayexpress

Timing of cortical interneuron migration is influenced by the cortical hem.

Project description:Cerebral cortical ?-aminobutyric acid (GABA)ergic interneurons originate from the basal forebrain and migrate into the cortex in 2 phases. First, interneurons cross the boundary between the developing striatum and the cortex to migrate tangentially through the cortical primordium. Second, interneurons migrate radially to their correct neocortical layer position. A previous study demonstrated that mice in which the cortical hem was genetically ablated displayed a massive reduction of Cajal-Retzius (C-R) cells in the neocortical marginal zone (MZ), thereby losing C-R cell-generated reelin in the MZ. Surprisingly, pyramidal cell migration and subsequent layering were almost normal. In contrast, we find that the timing of migration of cortical GABAergic interneurons is abnormal in hem-ablated mice. Migrating interneurons both advance precociously along their tangential path and switch prematurely from tangential to radial migration to invade the cortical plate (CP). We propose that the cortical hem is responsible for establishing cues that control the timing of interneuron migration. In particular, we suggest that loss of a repellant signal from the medial neocortex, which is greatly decreased in size in hem-ablated mice, allows the early advance of interneurons and that reduction of another secreted molecule from C-R cells, the chemokine SDF-1/CXCL12, permits early radial migration into the CP.

| S-EPMC3059882 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data