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Protocadherin 8 and transcription factor Dbx1 regulate the formation of developing cerebral cortex

ABSTRACT: Protocadherin 8 and transcription factor Dbx1 regulate the formation of developing cerebral cortex

PROVIDER: PRJNA955124 | ENA |

REPOSITORIES: ENA

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Protocadherin 8 and transcription factor Dbx1 regulate the formation of developing cerebral cortex

Project description:Normal development of the mammalian central nervous system requires correct tissue patterning, production of the appropriate cell types and establishment of functional neuronal circuits. Transcription factors (TFs) play essential roles in these processes, regulating the expression of target genes responsible for neuronal subtypes specific features. Cell adhesion molecules are key components of neuronal identities that control cell sorting, migration, neurite outgrowth/guidance and synaptogenesis. So far, the link between cell adhesion and cell fate is not known TFs are known to control neuronal adhesion but not the opposite. Here, using acute gain- and loss-of-function experiments by in utero electroporation in the developing mouse telencephalon we demonstrate that ectopic expression of Dbx1, a homeodomain TF acting as a cell fate determinant, leads to increased expression of Protocadherin 8 (Pcdh8) and cell aggregation, together with the induction of neuronal fate markers Nr4a2 (Nurr1) and Pax6. These effects were are modulated depending on the region and timing of electroporation. Furthermore, we found that Pcdh8 expression is required for Dbx1-induced fate specification. Surprisingly, Pcdh8 overexpression also proved sufficient to induce Dbx1 expression as well as a complete reorganisation of the apico-basal polarity and dorso-ventral patterning. Finally, we present evidence that these effects are mediated through regulation of the expression of Notch ligands and promotion of cell cycle exit. Altogether, our work therefore points to cell adhesion molecules as unexpectedimportant, yet unexpected important, players in the regulation of cell identity and, in particular, Pcdh8 through its bidirectional action crossregulation with the Dbx1 transcription factor.

2024-10-13 | GSE229603 | GEO

Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex [RNA-seq]

Project description:Special AT-rich sequencebinding protein 2 (SATB2) is essential for the development of cerebral cortex and key molecular node for the establishment of proper neural circuitry and function. Mutations in SATB2 gene lead to SATB2-associated syndrome (SAS), which is characterized by abnormal development of skeleton and central nervus system. We generated Satb2 knockout mouse model through CRISPR-Cas9 technology and performed RNA-seq and ChIP-seq of embryonic cerebral cortex. We conducted RT-qPCR, western blot, immunofluorescence staining, luciferase reporter assay and behavioral analysis for experimental verification.

2022-08-25 | GSE201561 | GEO

Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex [ChIP-seq]

2022-08-23 | GSE201433 | GEO

Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex

Project description:Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex

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Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution

Project description:In this study, we map chromatin accessibility and gene expression at single-cell resolution in the developing human cerebral cortex.

2021-03-31 | GSE162170 | GEO

Multiple parallel cell lineages in the developing mammalian cerebral cortex

Project description:Multiple parallel cell lineages in the developing mammalian cerebral cortex

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Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex [RNA-seq]

Project description:Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex [RNA-seq]

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Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex [ChIP-seq]

Project description:Downstream targeted genes of Satb2 regulate synaptic formation and axonogenesis in developing cerebral cortex [ChIP-seq]

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Effects of loss and gain of KAT6B on gene expression in the developing cerebral cortex [Myst4_RNAseq]

Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in the developing cerebral cortex. We isolated RNA from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, and from the E15.5 foetal cortex of mouse embryos and foetuses that lacked KAT6B or overexpressed KAT6B. Genes required for brain development and neuronal differentiation were downregulated in Kat6b null tissues and upregulated in Kat6b transgenic overexpressing tissue.

2024-11-06 | GSE280784 | GEO

Patterns of gene expression and evolution in the human developing cerebral cortex

Project description:The cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown. In order to uncover genetic networks underlying the development of the human cerebral cortex, we profiled the transcriptome of human fetal cortical domains containing language areas of Broca and Wernicke, as well as associative areas. We thus identified hundreds of genes displaying differential expression between the two areas or between distinct temporal stages. A subset of these genes was further validated by qRTPCR and in situ hybridization, revealing novel patterns of area and layer-specific expression throughout the developing cortex at midgestation, a critical period of cortical patterning. Computational genomic analyses revealed that the proportion of genes located close to evolutionarily accelerated regions was far more abundant among the genes differentially expressed between the two cortical areas examined, but not among those differentially expressed between different stages of development. In silico screening enabled to identify accelerated regions displaying increased turnover of change in transcription factor binding sites, which were enriched among those closer to genes differentially expressed between cortical areas. Overall our work points to the identification of cortical genes that display a unique combination of patterns of evolution and expression, which may constitute an important part of the genetic framework underlying human-specific neural traits and diseases. We determined gene expression patterns in cortical domains that contain areas thought to have undergone significant divergence during primate evolution, including language areas of Broca and Wernicke, as well as association areas of the frontal and parieto-temporal cortex in the right and left sides of human fetal brains at 17 and 19 gestional weeks.

2011-06-01 | E-GEOD-21858 | biostudies-arrayexpress

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