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Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons

ABSTRACT: Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons

PROVIDER: PRJNA909276 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22549920.fastq.gz	Fastqsanger.gz
	SRR22549921.fastq.gz	Fastqsanger.gz
	SRR22549922.fastq.gz	Fastqsanger.gz

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Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons

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

Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons [scRNA-Seq]

Project description:Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneity in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.

2021-02-05 | GSE166014 | GEO

Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons [RNA-Seq]

2021-02-05 | GSE166012 | GEO

Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons [ChIP-Seq]

2021-02-05 | GSE166011 | GEO

Postnatal persistence of hippocampal Cajal-Retzius cells has a crucial role in the establishment of the hippocampal circuit

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

Postnatal persistence of hippocampal Cajal-Retzius cells has a critical role in the establishment of the hippocampal circuit

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

Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis

Project description:Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis

| PRJNA1154552 | ENA

Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons

Project description:Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons

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Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis

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

Fate plasticity of interneuron specification

Project description:Fate plasticity of interneuron specification

| PRJNA1167741 | ENA