Mus musculus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1135791 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In the mammalian neocortex, excitatory neurons that send projections via the corpus callosum are critical to integrating information across the two brain hemispheres. The molecular mechanisms governing the development of the dendritic arbours and spines of these callosal neurons are poorly understood, yet these features are critical to their physiological properties. LIM Homeodomain 2 (Lhx2), a regulator of fundamental processes in cortical development, is expressed in postmitotic callosal neurons occupying layer II/III of the neocortex and also in their progenitors in the embryonic day (E) 15.5 ventricular zone of the mouse neocortex. We tested whether this factor is essential for dendritic arbour configuration and spine morphogenesis of layer II/III neurons. Here, we report loss of Lhx2 either in postmitotic callosal neurons or their progenitors, resulting in shrunken dendritic arbours and perturbed spine morphology. In postmitotic neurons, we identified that LHX2 regulates dendritic and spine morphogenesis via the canonical Wnt/β Catenin signalling pathway. Constitutive activation of this pathway in postmitotic neurons recapitulates the Lhx2 loss-of-function phenotype. In E15.5 progenitors, we identified that bHLH transcription factor Neurog2 mediates LHX2 function in regulating dendritic and spine morphogenesis. We show that Neurog2 expression increases upon loss of Lhx2 and that shRNA-mediated Neurog2 knockdown rescues the loss of Lhx2 phenotype. Our study uncovers novel LHX2 functions consistent with its temporally dynamic and multifunctional roles in the cortical circuit assembly.
2025-05-25 | GSE253914 | GEO
Project description:LHX2 regulates dendritic morphogenesis in layer II/III of the neocortex via distinct pathways in progenitors and postmitotic neurons
| PRJNA1067660 | ENA
Project description:Radial glial progenitor cells (RGCs) in the dorsal forebrain directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single cell RNA sequencing, we have studied gene expression patterns of two subtypes of RGCs that differ in their neurogenic behavior. One progenitor type rapidly produces postmitotic neurons, whereas the second progenitor remains relatively quiescence before generating neurons. We have identified candidate genes that are differentially expressed between these RGCs progenitor subtypes, including the transcription factor Sox9. Using in utero electroporation, we demonstrate that elevated Sox9 expression in progenitors prevents RGC division and leads to the generation of upper-layer cortical neurons from these progenitors at later ages. Our data thus reveal molecular differences between cortical progenitors with different neurogenic behavior and indicates that Sox9 is critical for the maintenance of RGCs to regulate the generation of upper layer neurons.
2021-06-29 | GSE179070 | GEO
Project description:In the developing vertebrate central nervous system, neurons and glia typically arise sequentially from common progenitors. Here, we report that the transcription factor Forkhead Box G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and in postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway component Fgfr3, that is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic ligand FGF18 in newborn neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons increases Fgf18 expression and enhances gliogenesis in the progenitors. These results fit well with the model that newborn neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex.
2025-01-15 | GSE253919 | GEO
Project description:Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex
| PRJNA127649 | ENA
Project description:In the developing cerebral cortex different types of neurons and glial cells are born through a precisely controlled sequence of events. The fate of cortical progenitors, in turn, is determined by an elusive conundrum of temporally and spatially regulated signalling mechanisms. We found the DNA-binding transcription factor Sip1 (also known as Zfhx1b) to be produced at high levels in postmitotic neurons of the cerebral cortex. Conditional deletion of Sip1 in young neocortical neurons was found to induce premature and increased production of upper layer neurons at the expense of deep layer neurons. Furthermore, it caused precocious and increased generation of glial precursors during late corticogenesis, leading subsequently to enhanced astrocytogenesis at early postnatal stages. Expression profiling analysis indicated that the temporal shift in upper layer production coincides with overexpression of the neurotrophin-3 (NT3) gene and altered growth factor signalling in progenitors, while the premature gliogenesis is preceded by upregulation of fibroblast growth factor-9 (Fgf9) gene expression. Chromatin immunoprecipitation and in situ hybridization validates NT3 as a direct target of Sip1 in the cortex and confines the transcriptional repression by Sip1 to postmitotic neurons. Moreover, we show that exogenous application of Fgf9 in solution or via coated beads to wild-type cortical slices induces premature and excessive generation of glial precursors in the germinal zone. In conclusion, our data suggest that throughout corticogenesis Sip1 acts to restrain the level of production of secreted signalling factors in postmitotic neurons. These factors feed back to progenitor cells in order to regulate the timing of cell fate switch and the numbers of neurons and glial cells produced in the developing cerebral cortex.
2009-10-30 | GSE16699 | GEO
Project description:Inactivation of ERK/MAPK signaling in developing postmitotic cortical excitatory neurons results in a significent loss of Ctip2 positive layer 5 neurons and axon projections. Microarray dada revealed the reduced levels of a vast majority of layer V specific transcripts.
2016-02-02 | GSE75129 | GEO
Project description:Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. The regulatory strategies that neurons use during progressive development and maturation remain unclear. We present an integrated single-cell epigenomic and transcriptional analysis of individual classes of neurons from both mouse and marmoset neocortex, sampled during both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We find that in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use molecular regulatory programs with broader tissue distribution and greater evolutionary conservation. In contrast, programs that are active during later neuronal maturation implement more brain- and neuron-specific mechanisms showing greater evolutionary divergence. Our work uncovers a temporally-regulated shift in regulatory choices, likely reflecting unique evolutionary constraints on distinct events of neuronal development in the neocortex.
2022-05-31 | GSE204850 | GEO
Project description:Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. The regulatory strategies that neurons use during progressive development and maturation remain unclear. We present an integrated single-cell epigenomic and transcriptional analysis of individual classes of neurons from both mouse and marmoset neocortex, sampled during both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We find that in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use molecular regulatory programs with broader tissue distribution and greater evolutionary conservation. In contrast, programs that are active during later neuronal maturation implement more brain- and neuron-specific mechanisms showing greater evolutionary divergence. Our work uncovers a temporally-regulated shift in regulatory choices, likely reflecting unique evolutionary constraints on distinct events of neuronal development in the neocortex.
2022-05-31 | GSE204761 | GEO
Project description:Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. The regulatory strategies that neurons use during progressive development and maturation remain unclear. We present an integrated single-cell epigenomic and transcriptional analysis of individual classes of neurons from both mouse and marmoset neocortex, sampled during both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We find that in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use molecular regulatory programs with broader tissue distribution and greater evolutionary conservation. In contrast, programs that are active during later neuronal maturation implement more brain- and neuron-specific mechanisms showing greater evolutionary divergence. Our work uncovers a temporally-regulated shift in regulatory choices, likely reflecting unique evolutionary constraints on distinct events of neuronal development in the neocortex.
2022-05-31 | GSE204760 | GEO