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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 [ChIP-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 | GSE166011 | 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 [scRNA-Seq]

2021-02-05 | GSE166014 | 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

Constitutive activation of canonical Wnt signaling in hem progenitors suppresses the fate of hem-derived Cajal-Retzius cells

Project description:Cajal-Retzius cells (CR cells) are the earliest born neurons in the cerebral cortex, and have been implicated in neuronal migration and development of cortical circuitry. One of the sources of CR cells is the cortical hem, which is rich in morphogens of the canonical WNT signaling family. In this study we examine the effect of stabilization of β-CATENIN (gain of function, GOF) in the mouse cortical hem and show that although neurons are still produced, they do not acquire a CR cell identity. The trajectory of differentiation examined using single-cell transcriptomics revealed that upon β-CATENIN GOF, hem-derived CR cells do not display a TBR2+ stage characteristic of immature CR cells. This effect is only seen when β-CATENIN GOF is driven in hem progenitors and is not seen upon β-CATENIN GOF in postmitotic CR cells. These data suggest that a TBR2+ stage may be important for hem-derived CR cell development and that this step appears to be sensitive to levels of stabilized β-CATENIN in hem progenitors.

2026-03-23 | GSE273962 | GEO

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

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Capicua regulates the survival of Cajal-Retzius cells in the postnatal hippocampus

Project description:Capicua regulates the survival of Cajal-Retzius cells in the postnatal hippocampus

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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

| PRJNA698977 | ENA

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