Similar Datasets
Project description:Short- and long-distance extrinsic regulation of interneuron specification and migration
| PRJNA837579 | ENA
Project description:Cortical interneuron diversity arises from the interplay of intrinsic developmental patterning and local extrinsic cues. While individual genetic programs underlying cardinal cell type identity are established in immature neurons prior to integration into cortical circuits, it remains unclear whether distinct interneuron subtype identities are pre-established, and if so, how their identity is maintained prior to circuit integration. Sox6 is a transcription factor with an established role in the maturation of interneurons derived from the medial ganglionic eminence and cell-type specification in other neuronal and non-neuronal cells. To determine a possible role in maintaining cortical somatostatin-expressing (Sst+) interneuron subtype identity, we conditionally removed Sox6 (Sox6-cKO) in migrating Sst+ interneurons and assessed the effects on their mature identity. In adolescent animals, five of eight molecular Sst+ subtypes were nearly absent in the cortex of Sox6-cKO mice. This reduced subtype diversity was not due to a decrease in the overall number of Sst+ interneurons and cells displayed electrophysiological maturity and expressed genes enriched within the broad class of Sst+ interneurons. Furthermore, we show that at embryonic day 18.5, prior to cortical integration, mature Sst+ cell subtype identity could already be inferred in both control and Sox6-cKO cortices, suggesting that the loss in subtype diversity observed in the mature cortex is due to a disrupted subtype maintenance. Importantly, Sox6 removal at postnatal day 7, after Sst+ interneurons have finished migrating and begun integration into the network, did not disrupt marker expression of Sst+ subtypes in the mature cortex. Therefore, Sox6 is necessary during this migratory phase for maintenance of Sst+ subtypes identity, indicating that subtype maintenance requires active transcriptional programs during migration.
2023-08-25 | GSE233791 | GEO
Project description:Interneurons navigate along multiple tangential paths to settle into appropriate cortical layer. They undergo saltatory migration, which is paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. However, it remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes deglutamylation, is a pivotal regulator of pausing of cortical interneurons. Moreover, we show that pausing during migration controls the flow of interneurons invading the cortex by generating heterogeinity in movement at the population level. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also secondarily impairs the generation of age-matched upper layer projection neurons.
2018-02-14 | PXD006397 | Pride
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
Project description:Here we show that regions of the honeybee brain involved in visual processing and learning and memory show a genomic response to distance information. Using a method that separates effects of perceived distance from effects of actual distance flown, we found that individuals forced to shift from a short to a perceived long distance to reach a feeding site showed differences in gene expression in the optic lobes and mushroom bodies relative to individuals that continued to perceive flying a short distance.
2011-03-05 | E-TABM-910 | biostudies-arrayexpress
Project description:To investigate the novel link between CP-AMPARs and excitability, we assessed global PV interneuron transcriptome changes with FICSR-seq (Fixation-Capture Single Cell RNA Recovery-seq) on forebrain PV interneurons. FACS-assisted PV interneuron bulk RNA-seq of PV-Cre;lsl-eGFP-GluA2 mice and PV-Cre;lsl-eGFP controls showed no expression changes in 278 out of 279 genes comprising the major classes of ion channels and excitatory/inhibitory synapse proteins. This lack of expression changes suggests a post-transcriptional regulation of intrinsic and extrinsic (synaptic) excitability. The exception was GluA2 mRNA, which was expressed ~2 fold compared to control PV interneurons, in agreement with protein measurements. GluA1, although downregulated at protein level, was unchanged at the mRNA level. These transcriptomic results suggest that the substantial changes in PV interneuron excitability after CP-AMPAR removal are not supported by changes in gene expression but likely reflect post-transcriptional regulation.
2024-07-05 | GSE262872 | GEO
Project description:Combinatorial transcription codes generate the myriad of cell types during development, and thus likely provide crucial insights into directed differentiation of stem cells to a specific cell type. The LIM-complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos. Here, we report that Isl1-Lhx3, a LIMcomplex-mimicking fusion, induces a signature of MN transcriptome and concomitantly suppresses interneuron differentiation programs, thereby serving as a potent and specific inducer of MNs in stem cells. We show that an equimolar ratio of Isl1 and Lhx3 and the LIM-domain of Lhx3 are crucial for generating MNs without upregulating interneuron genes. These led us to design Isl1-Lhx3, which maintains the desirable 1:1 ratio of Isl1 and Lhx3 and the LIM-domain of Lhx3. Isl1-Lhx3 drives MN differentiation with high specificity and efficiency in the spinal cord and embryonic stem cells, bypassing the need for sonic hedgehog. RNA-seq analysis revealed that Isl1-Lhx3 induces the expression of a battery of MN genes that control various functional aspects of MNs, while suppressing key interneuron genes. Our studies uncover a highly efficient method for directed MN generation and MN gene networks. Our results also demonstrate a general strategy of utilizing embryonic transcription complexes for producing specific cell types from stem cells. Examine the RNA expression profiles of inducible motor neurons-embryonic stem cells (iMN-ESCs) with or without Dox treatment, with biological duplicates.
2012-02-03 | E-GEOD-35510 | biostudies-arrayexpress
Project description:The mammalian cerebral cortex comprises a complex neuronal network that maintains a delicate balance between excitatory neurons and inhibitory interneurons. Previous studies, including our own research, have shown that specific interneuron subtypes are closely associated with particular pyramidal neuron types, forming stereotyped local inhibitory microcircuits. However, the developmental processes that establish these precise networks are not well understood. Here we show that pyramidal neuron types are instrumental in maintaining the terminal differentiation and survival of specific associated interneuron subtypes. In a wild-type cortex, the relative abundance of different interneuron subtypes aligns precisely with the pyramidal neuron types with which they synaptically target. In Fezf2 mutant cortex, characterized by the absence of layer 5 pyramidal tract neurons and an expansion of layer 6 intratelencephalic neurons, we observed a corresponding decrease in associated layer 5b interneurons and an increase in layer 6 subtypes. Interestingly, these shifts in composition are achieved through mechanisms that are specific to different interneuron types. While SST interneurons adjust their abundance to the change in pyramidal neuron prevalence through the regulation of programmed cell death, parvalbumin cells alter their identity. These findings illustrate two key strategies by which the dynamic interplay between pyramidal neurons and interneurons allows local microcircuits to be sculpted precisely. These insights underscored the precise roles of extrinsic signals from pyramidal cells in the establishment of interneuron diversity and their subsequent integration into local cortical microcircuits.
2024-08-15 | GSE272706 | GEO
Project description:Dynamic extrinsic pacing of the HOX clock in human axial progenitors control motor neuron subtype specification
| PRJNA642885 | ENA
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 interneuｒon 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.
2014-10-07 | GSE56996 | GEO