Bulk RNA sequencing of intracortically-projecting neurons at P10
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE122742 | GEO | 2018/11/21
REPOSITORIES: GEO
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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: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.
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2012-03-21 | E-GEOD-31613 | biostudies-arrayexpress
Project description:Bulk RNA sequencing of intracortically-projecting neurons at P10
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Project description:In the mammalian cerebral cortex, the developmental events governing the allocation of different classes of inhibitory neurons into distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 is upregulated in serotonin receptor 3a-expressing (HTR3A) cortical interneurons (hINs) as they invade the cortical plate and that it regulates their laminar allocation to superficial cortical layers. We find that the PlexinA4 ligand Semaphorin3A acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that Semaphorin3A specifically controls their laminar positioning through PlexinA4. We identify that deep layer interneurons constitute a major source of Semaphorin3A in the developing cortex and demonstrate that cell-type specific genetic deletion of Semaphorin3A in these interneurons specifically affects the laminar allocation of hINs. These data demonstrate that in the neocortex, deep layer interneurons control the laminar allocation of hINs into superficial layers.
2021-01-19 | GSE152271 | GEO
Project description:Genome-wide transcriptional profiling allows characterization of the molecular underpinnings of neocortical organization, including cortical areal specialization, laminar cell type diversity and functional anatomy. Microarray analysis of individual cortical layers across sensorimotor and association cortices in rhesus macaque demonstrated robust and specific laminar and areal molecular signatures driven by differential expression of genes associated with specialized neuronal function. Gene expression corresponding with laminar architecture was generally similar across cortical areas, although genes with robust areal patterning were often highly laminar as well, and these patterns were more highly conserved between macaque and human as compared to mouse. Layer 4 of primate primary visual cortex displayed a distinct molecular signature compared to other cortical regions, a specialization not observed in mouse. Overall, transcriptome-based relationships were strongest between proximal layers in a cortical area, and between neighboring areas along the rostrocaudal axis, reflecting in vivo cortical spatial topography and therefore a developmental imprint.
2012-03-21 | GSE31613 | GEO
Project description:A hallmark of cortical evolution is the high dynamic subventricular zone (SVZ) expansion, where basal progenitors (BPs) amplify and neuronal transcriptional programs unfold. How non-coding molecular factors such as microRNAs influence these developmental trajectories and regulate the acquisition of cortical type identities is largely unknown. Here we demonstrate that miR-137 and miR-122 regulate the positioning and identity features of superficial layer cortical neurons by acting at distinct steps of their developmental trajectories. MiR-137 sustains basal progenitor amplification by reverting their neurogenic commitment and inducing high proliferative state upregulating Cd63 and inhibiting Myt1l. Cd63 is an extra-cellular matrix (ECM) receptor which interacts with b3- and 1-integrin pathways to promote proliferation, while Myt1l is a transcription factor that promotes and sustains neuronal fate. The BPs amplification by miR-137 is converted in the promotion of intracortical projecting neuron (ICPN) identity and L2/3 expansion. As opposed to miR-137, miR-122 acts postmitotically, affecting the bioelectrical properties, the calcium and cytoskeleton dynamics of newborn neurons as well as their transcriptional program, leading to a persistent molecular immaturity across time. Overall, these findings reveal that miR-137 and miR-122 are key regulators of the developmental trajectory of cortical neurons across evolution.
2022-03-09 | GSE159596 | GEO
Project description:Neural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations.
2014-12-01 | GSE63300 | GEO
Project description:Purpose:This work aimed to identify the genetic profiles of piriform projection neurons and characterize their spatial organization within the piriform cortex. Methods: We microdissected the three layers of pirifrom cortex by laser capture (LMD) and performed RNA deep sequencing in order to identify layer-specific molecular markers, we then validated these data by using RNA in situ hybridization and immunohistochemistry.We next performed anterograde neural tracing experiments to identify piriform target regions, and retrograde neural tracing experiments to analyze how piriform projection neurons are organized within piriform cortex.We then combined the analysis of patterns of gene expression with retrograde tracing experiments to identify molecular signatures of the different subclasses of piriform projecting neurons. Results:We show that layers and sub-layers of the piriform cortex can be discriminated by gene expression patterns in adult piriform cortex. We observe that neurons projecting to distinct target areas are localized in distinct layers and express specific genes. We demonstrate that these molecular signatures of piriform projection neurons are maintained in reeler mice, in which cortical lamination is lost and neural positioning is scrambled, suggesting that piriform output connectivity strictly depends on the molecular programm, rather than a proper lamination of the cortex. Conclusion:These results provide important insights into the principles underling the piriform connectivity.
2016-07-13 | GSE70800 | GEO