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LSD1 Corepressor Rcor2 Orchestrates Neurogenesis in the Developing Mouse Brain

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE75040 | GEO | 2016/01/22

SECONDARY ACCESSION(S): PRJNA302273

REPOSITORIES: GEO

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LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain.

Project description:Epigenetic regulatory complexes play key roles in the modulation of transcriptional regulation underlying neural stem cell (NSC) proliferation and progeny specification. How specific cofactors guide histone demethylase LSD1/KDM1A complex to regulate distinct NSC-related gene activation and repression in cortical neurogenesis remains unclear. Here we demonstrate that Rcor2, a co-repressor of LSD1, is mainly expressed in the central nervous system (CNS) and plays a key role in epigenetic regulation of cortical development. Depletion of Rcor2 results in reduced NPC proliferation, neuron population, neocortex thickness and brain size. We find that Rcor2 directly targets Dlx2 and Shh, and represses their expressions in developing neocortex. In addition, inhibition of Shh signals rescues the neurogenesis defects caused by Rcor2 depletion both in vivo and in vitro. Hence, our findings suggest that co-repressor Rcor2 is critical for cortical development by repressing Shh signalling pathway in dorsal telencephalon.

| S-EPMC4736047 | biostudies-literature

LSD1 Corepressor Rcor2 Orchestrates Neurogenesis in the Developing Mouse Brain [ChIP-Seq]

Project description:ChIP-seq analysis using Flag M2, LSD1 and H3K4me2 antibodies respectively in Rcor2Flag embryonic brain.

2016-01-22 | GSE75039 | GEO

LSD1 Corepressor Rcor2 Orchestrates Neurogenesis in the Developing Mouse Brain [RNA-Seq]

Project description:RNA-seq analysis of Rcor2fl/fl and Rcor2cko embryonic cortex.

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LSD1 Corepressor Rcor2 Orchestrates Neurogenesis in the Developing Mouse Brain

Project description:LSD1 Corepressor Rcor2 Orchestrates Neurogenesis in the Developing Mouse Brain

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LSD1-RCOR2 binding and LSD1 and BRD9 transcriptome analysis in Merkel cell carcinoma cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex

Project description:The role of WNT/β-catenin signalling in mouse neocortex development remains ambiguous. Most studies demonstrate that WNT/β-catenin regulates progenitor self-renewal but others suggest it can also promote differentiation. Here we explore the role of WNT/STOP signalling, which stabilizes proteins during G2/M by inhibiting glycogen synthase kinase (GSK3)-mediated protein degradation. We show that mice mutant for cyclin Y and cyclin Y-like 1 (Ccny/l1), key regulators of WNT/STOP signalling, display reduced neurogenesis in the developing neocortex. Specifically, basal progenitors, which exhibit delayed cell-cycle progression, were drastically decreased. Ccny/l1-deficient apical progenitors show reduced asymmetric division due to an increase in apical-basal astral microtubules. We identify the neurogenic transcription factors Sox4 and Sox11 as direct GSK3 targets that are stabilized by WNT/STOP signalling in basal progenitors during mitosis and that promote neuron generation. Our work reveals that WNT/STOP signalling drives cortical neurogenesis and identifies mitosis as a critical phase for neural progenitor fate.

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Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex.

Project description:The role of WNT/β-catenin signalling in mouse neocortex development remains ambiguous. Most studies demonstrate that WNT/β-catenin regulates progenitor self-renewal but others suggest it can also promote differentiation. Here we explore the role of WNT/STOP signalling, which stabilizes proteins during G2/M by inhibiting glycogen synthase kinase (GSK3)-mediated protein degradation. We show that mice mutant for cyclin Y and cyclin Y-like 1 (Ccny/l1), key regulators of WNT/STOP signalling, display reduced neurogenesis in the developing neocortex. Specifically, basal progenitors, which exhibit delayed cell cycle progression, were drastically decreased. Ccny/l1-deficient apical progenitors show reduced asymmetric division due to an increase in apical-basal astral microtubules. We identify the neurogenic transcription factors Sox4 and Sox11 as direct GSK3 targets that are stabilized by WNT/STOP signalling in basal progenitors during mitosis and that promote neuron generation. Our work reveals that WNT/STOP signalling drives cortical neurogenesis and identifies mitosis as a critical phase for neural progenitor fate.

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Snip1 and PRC2 coordinate the intrinsic apoptosis, cell division, and neurogenesis in the developing brain

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-12 | GSE212445 | GEO

Mouse neurogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

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PRDM16 orchestrates angiogenesis via neural differentiation in the developing brain.

Project description:Angiogenesis plays crucial roles in maintaining the complex operation of central nervous system (CNS) development. The architecture of communication between neurogenesis and angiogenesis is essential to maintain normal brain development and function. Hence, any disruption of neuron-vascular communications may lead to the pathophysiology of cerebrovascular diseases and blood-brain barrier (BBB) dysfunction. Here we demonstrate that neural differentiation and communication are required for vascular development. Regarding the cellular and molecular mechanism, our results show that PRDM16 activity determines the production of mature neurons and their specific positions in the neocortex. In the cortical plate (CP), aberrant neurons fail to secrete modular calcium-binding protein 1 (SMOC1), an important neuronal signal that participates in neurovascular communication to regulate CNS angiogenesis. Neuronal SMOC1 interacts with TGFBR1 by activating the transcription factors phospho-Smad2/3 to convey intercellular signals to endothelial cells (ECs) in the TGF-β-Smad signaling pathway. Together, our results highlight a crucial coordinated neurovascular development process orchestrated by PRDM16 and reveal the importance of intimate communication for building the neurovascular network during brain development.

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