Poly (ADP-Ribose) Polymerase 1 Regulates Cajal-Retzius Cell Development and Neural Precursor Cell Adhesion
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ABSTRACT:
PROVIDER: PRJNA721198 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR14208944.fastq.gz | Fastqsanger.gz | |||
| SRR14208945.fastq.gz | Fastqsanger.gz | |||
| SRR14208946.fastq.gz | Fastqsanger.gz | |||
| SRR14208947.fastq.gz | Fastqsanger.gz | |||
| SRR14208948.fastq.gz | Fastqsanger.gz |
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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: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.
| S-EPMC8542860 | 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: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:Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis
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Project description:Capicua regulates the survival of Cajal-Retzius cells in the postnatal hippocampus
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Project description:Key nuclear processes in eukaryotes including DNA replication or repair and gene regulation require extensive chromatin remodeling catalyzed by energy consuming enzymes. How the energetic demands of such processes are ensured in response to rapid stimuli remains unclear. We have analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly-ADP-ribose to ADP-ribose. Nuclear ATP synthesis requires the combined enzymatic activities of PARP1, PARG and NUDIX5/NUDT5. Although initiated via mitochondrial derived ATP, the nuclear source of ATP is essential for hormone induced chromatin remodeling, gene regulation and cell proliferation and may also participate in DNA repair. This novel pathway reveals exciting avenues of research for drug development.
2017-12-23 | GSE64467 | GEO
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:Protein ADP-ribosylation is a covalent, reversible post-translational modification that has important functions in several cellular mechanisms. The identification of modified proteins in cells has proven challenging and, due to the low abundance of protein ADP-ribosylation, has mainly been possible via enrichment methodologies using ADP-ribose binding domains. Here, using random mutagenesis and in vitro selection with an ADP-ribosylated histone peptide, we engineered the archaeal Af1521 macro domain to generate an engineered isoform containing nine mutations that displays significantly increased affinity towards ADP-ribose. Comparison of the wild-type and the engineered Af1521 macro domains using our proteomic ADP-ribosylome enrichment workflow demonstrated an increased identification rate of ADP-ribosylated proteins with the engineered Af1521.
2020-10-20 | PXD016686 | Pride
Project description:Programmed cell death is crucial for organ morphogenesis and tissue homeostasis. Understanding programmed cell death in the developing brain is essential for comprehending both normal brain development and neurological disorders. In this study, we utilize Cajal-Retzius (CR) cells, transient neurons that populate the embryonic cortex and are predominantly eliminated in early postnatal stages, as a model to investigate the regulation of programmed cell death. While many CR cells typically undergo postnatal cell death, some persist into adulthood in the hippocampus, influencing local circuits and behaviors. Here, we show that the loss of capicua (CIC), a transcriptional repressor implicated in a rare neurodevelopmental syndrome and multiple cancers, results in aberrant survival of CR cells in the adult hippocampus. Altered cell survival is mediated by the cell-autonomous function of CIC in hippocampal CR cells. Surprisingly, the atypical persistence of CR cells following CIC loss does not impact hippocampal-dependent behaviors or susceptibility to kainic acid-induced seizures. Single-cell transcriptomic analysis unveils previously unrecognized heterogeneity among hippocampal CR cells and suggests a role of CIC in repressing Fgf1 expression. Additionally, we reveal that FGF1 and BCL2 serve as pivotal regulators enhancing CR cell survival in the postnatal hippocampus. Our findings shed light on a previously unacknowledged role of CIC upstream of FGF signaling and elucidate the apoptosis mechanism governing developmental programmed CR cell death.
2025-10-16 | GSE309238 | GEO