Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis
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PROVIDER: PRJNA1154552 | ENA |
REPOSITORIES: ENA
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Project description:Cajal-Retzius cells (CRs) are a peculiar neuronal type within the developing mammalian cerebral cortex. One of their best documented feature is the robust secretion of Reln, a glycoprotein essential for the establishment of cortical layers through the control of radial migration of glutamatergic neurons. Although CRs and Reln are tightly associated, a direct assessment of their relative contribution to cortical morphogenesis is still lacking. Here we took advantage of the Gmnc-/- mouse model, in which CRs are initially produced but abnormally specified and undergo early apoptosis leading to a severe depletion, to investigate the consequences of CRs loss on neocortical lamination and hippocampal morphogenesis. We then compared to the phenotype of CRs-specific conditional Reln deletion in order to evaluate the relative contribution of CRs and Reln. We found that neocortical lamination defects upon CRs depletion are relatively modest, and partially recapitulated by Reln loss. By contrast, hippocampal morphogenesis was far more affected by CRs depletion than Reln loss. In addition, we found the lateral cortex especially sensitive to CRs depletion, but not Reln loss. These data support a model whereby CRs-derived Reln and Reln-independent signals differentially contribute to the morphogenesis of distinct regions of the developing cortex.
2024-09-04 | GSE276037 | GEO
Project description:We have previously described hypomorphic reelin (Reln) mutant mice, RelnCTRdel, in which the morphology of the dentate gyrus is distinct from that seen in reeler mice. In the RelnCTRdel mutant, the infrapyramidal blade of the dentate gyrus fails to extend, while the suprapyramidal blade forms with a relatively compact granule neuron layer. Underlying this defect, we now report several developmental anomalies in the RelnCTRdel dentate gyrus. Most strikingly, the distribution of Cajal-Retzius cells was aberrant; Cajal-Retzius neurons were increased in the suprapyramidal blade, but were greatly reduced along the subpial surface of the prospective infrapyramidal blade. We also observed multiple abnormalities of the fimbriodentate junction. Firstly, progenitor cells were distributed abnormally; the "neurogenic cluster" at the fimbriodentate junction was absent, lacking the normal accumulation of Tbr2-positive intermediate progenitors. However, the number of dividing cells in the dentate gyrus was not generally decreased. Secondly, a defect of secondary glial scaffold formation, limited to the infrapyramidal blade, was observed. The densely radiating glial fibers characteristic of the normal fimbriodentate junction were absent in mutants. These fibers might be required for migration of progenitors, which may account for the failure of neurogenic cluster formation. These findings suggest the importance of the secondary scaffold and neurogenic cluster of the fimbriodentate junction in morphogenesis of the mammalian dentate gyrus. Our study provides direct genetic evidence showing that normal RELN function is required for Cajal-Retzius cell positioning in the dentate gyrus, and for formation of the fimbriodentate junction to promote infrapyramidal blade extension.
| S-EPMC7558149 | biostudies-literature
Project description:Cajal-Retzius (CR) cells are a transient type of neurons that populate the postnatal hippocampus. The role of transient cell types and circuits have been vastly addressed in neocortical regions, but poorly studied in the hippocampus. To understand how CR cells persistence influences the maturation of hippocampal circuits, we specifically ablated CR cells from the postnatal hippocampus.
2023-12-15 | GSE201886 | GEO
Project description:The extracellular protein Reelin, expressed by Cajal-Retzius (CR) cells at early stages of cortical development and at late stages by GABAergic interneurons, regulates radial migration and the "inside-out" pattern of positioning. Current models of Reelin functions in corticogenesis focus on early CR cell-derived Reelin in layer I. However, developmental disorders linked to Reelin deficits, such as schizophrenia and autism, are related to GABAergic interneuron-derived Reelin, although its role in migration has not been established. Here we selectively inactivated the Reln gene in CR cells or GABAergic interneurons. We show that CR cells have a major role in the inside-out order of migration, while CR and GABAergic cells sequentially cooperate to prevent invasion of cortical neurons into layer I. Furthermore, GABAergic cell-derived Reelin compensates some features of the reeler phenotype and is needed for the fine tuning of the layer-specific distribution of cortical neurons. In the hippocampus, the inactivation of Reelin in CR cells causes dramatic alterations in the dentate gyrus and mild defects in the hippocampus proper. These findings lead to a model in which both CR and GABAergic cell-derived Reelin cooperate to build the inside-out order of corticogenesis, which might provide a better understanding of the mechanisms involved in the pathogenesis of neuropsychiatric disorders linked to abnormal migration and Reelin deficits.
| S-EPMC9477240 | biostudies-literature
Project description:Poly (ADP-Ribose) Polymerase 1 (PARP1) is a ubiquitously expressed enzyme that regulates DNA damage repair, cell death, inflammation, and transcription. PARP1 functions by adding ADP-ribose polymers (PAR) to proteins including itself, using NAD+ as a donor. This post-translational modification known as PARylation results in changes in the activity of PARP1 and its substrate proteins and has been linked to the pathogenesis of various neurological diseases. PARP1 KO mice display schizophrenia-like behaviors, have impaired memory formation, and have defects in neuronal proliferation and survival, while mutations in genes that affect PARylation have been associated with intellectual disability, psychosis, neurodegeneration, and stroke in humans. Yet, the roles of PARP1 in brain development have not been extensively studied. We now find that loss of PARP1 leads to defects in brain development and increased neuronal density at birth. We further demonstrate that PARP1 loss increases the expression levels of genes associated with neuronal migration and adhesion in the E15.5 cerebral cortex, including Reln. This correlates with an increased number of Cajal-Retzius (CR) cells in vivo and in cultures of embryonic neural progenitor cells (NPCs) derived from the PARP1 KO cortex. Furthermore, PARP1 loss leads to increased NPC adhesion to N-cadherin, like that induced by experimental exposure to Reelin. Taken together, these results uncover a novel role for PARP1 in brain development, i.e., regulation of CR cells, neuronal density, and cell adhesion.
2021-09-16 | GSE171852 | GEO
Project description:Cajal-Retzius (CR) cells are a transient neuron type that populate the postnatal hippocampus. The role of transient cell types and circuits have been vastly addressed in neocortical regions, but poorly studied in the hippocampus. To understand how CR cells persistence influences the maturation of hippocampal circuits, we specifically ablated CR cells from the postnatal hippocampus. We observed layer-specific changes in the dendritic complexity and spine density of CA1 pyramidal cells. We were able to identify significant changes in the expression levels of Latrophilin-2, a postsynaptic guidance molecule known for its role in the entorhinal-hippocampal connectivity. Those findings were supported by changes in the overall synaptic proteomic content in CA1 Stratum Lacunosum-Moleculare.
2024-05-24 | PXD042517 | Pride
Project description:Cajal-Retzius (CR) neurons are key players of cortical development that display a very unique transcriptomic identity. However, little is known about the mechanisms involved in their fate specification. Here we use scRNAseq to reconstruct the differentiation trajectory of hem-derived CR cells (CRs) and unravel the transient expression of a complete gene module previously known to control the cellular process of multiciliogenesis. However, we find that CRs do not undergo centriole amplification or multiciliation. We show that upon genetic disruption of Gmnc, the master regulator of the multiciliation cascade, CRs are initially produced but fail to reach their normal identity and lean towards an aberrant fate resulting in their massive apoptosis. We further dissect the contribution of multiciliation effector genes and identify Trp73 as a key determinant. Finally, we use in utero electroporation to demonstrate that the intrinsic competence of hem progenitors as well as the heterochronic expression of Gmnc prevent centriole amplification in the CR lineage. Our work exemplifies how the co-option of a complete gene module, repurposed to control a completely distinct process, may contribute to the emergence of novel cell identities.
2023-06-01 | GSE220237 | GEO
Project description:Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons
| PRJNA909276 | ENA
Project description:Cajal-Retzius cells have important role in cerebral cortex development, such as secreted Reln protein, maintain normal lays of cerebral cortex. To explore novel secretory protein of Cajal-Retzius cells and to survey the roles of Cajal-Retzius cells in cerebral cortex development, we analyzed transcriptome profiles of 6753 single cells of the embryonic 18 days.
2019-11-27 | GSE123035 | GEO
Project description:Poly (ADP-Ribose) Polymerase 1 Regulates Cajal-Retzius Cell Development and Neural Precursor Cell Adhesion
| PRJNA721198 | ENA