An epigenetic circuit controls neurogenic programs during neocortex development

Development ◽  
2021 ◽  
Vol 148 (22) ◽  
Author(s):  
Andi Wang ◽  
Junbao Wang ◽  
Kuan Tian ◽  
Dawei Huo ◽  
Hanzhe Ye ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Remodeling ◽  
Adult Neurogenesis ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Projection Neurons ◽  
Genomic Locus ◽  
Intermediate Progenitors ◽  
Chromatin Remodeling Complex ◽  
Non Coding Rna

ABSTRACT The production and expansion of intermediate progenitors (IPs) are essential for neocortical neurogenesis during development and over evolution. Here, we have characterized an epigenetic circuit that precisely controls neurogenic programs, particularly properties of IPs, during neocortical development. The circuit comprises a long non-coding RNA (LncBAR) and the BAF (SWI/SNF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains more deep-layer but fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production, but paradoxically prolongs the duration of the cell cycle of IPs during mid-later neocortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage results in fewer adult neural progenitor cells in the subventricular zone of lateral ventricles, leading to a failure in adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the BAF chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with the genomic locus of, and suppresses the expression of, Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 overexpression in LncBAR-knockout neural precursors reverses compromised cell cycle progressions of IPs.

scholarly journals Histone chaperone HIRA regulates neural progenitor cell proliferation and neurogenesis via β-catenin

2017 ◽  
Vol 216 (7) ◽  
pp. 1975-1992 ◽  
Author(s):  
Yanxin Li ◽  
Jianwei Jiao
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Histone Chaperone ◽  
Epigenetic Mechanism ◽  
Progenitor Cell Proliferation ◽  
Early Neurogenesis

Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or β-catenin can override neurogenesis abnormities caused by HIRA defects. Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates β-catenin expression and then regulates neurogenesis. This finding represents a novel epigenetic mechanism underlying the histone code and has profound and lasting implications for diseases and neurobiology.

Chemokine receptor CXCR4 signaling modulates the growth factor-induced cell cycle of self-renewing and multipotent neural progenitor cells

Glia ◽  
2010 ◽  
Vol 59 (1) ◽  
pp. 108-118 ◽  
Author(s):  
Meizhang Li ◽  
Cathleen J. Chang ◽  
Justin D. Lathia ◽  
Li Wang ◽  
Holly L. Pacenta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Chemokine Receptor ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Cxcr4 Signaling ◽  
Chemokine Receptor Cxcr4

Cell cycle progression is required for nuclear migration of neural progenitor cells

2006 ◽  
Vol 1088 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Masaki Ueno ◽  
Kei-ichi Katayama ◽  
Hirofumi Yamauchi ◽  
Hiroyuki Nakayama ◽  
Kunio Doi
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Neural Progenitor Cells ◽  
Nuclear Migration ◽  
Neural Progenitor ◽  
Cycle Progression

scholarly journals Hippocampal Adult Neurogenesis Is Maintained by Neil3-Dependent Repair of Oxidative DNA Lesions in Neural Progenitor Cells

Cell Reports ◽  
2012 ◽  
Vol 2 (3) ◽  
pp. 503-510 ◽  
Author(s):  
Christine Elisabeth Regnell ◽  
Gunn Annette Hildrestrand ◽  
Yngve Sejersted ◽  
Tirill Medin ◽  
Olve Moldestad ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Adult Neurogenesis ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Dna Lesions

scholarly journals Sfh1p, a component of a novel chromatin-remodeling complex, is required for cell cycle progression.

1997 ◽  
Vol 17 (6) ◽  
pp. 3323-3334 ◽  
Author(s):  
Y Cao ◽  
B R Cairns ◽  
R D Kornberg ◽  
B C Laurent
Keyword(s):  
Cell Cycle ◽  
Chromatin Remodeling ◽  
Cell Cycle Progression ◽  
Normal Function ◽  
Temperature Sensitive ◽  
Cycle Progression ◽  
Conserved Domain ◽  
Chromatin Remodeling Complex ◽  
Evolutionarily Conserved ◽  
M Phase

Several eukaryotic multiprotein complexes, including the Saccharomyces cerevisiae Snf/Swi complex, remodel chromatin for transcription. In contrast to the Snf/Swi proteins, Sfh1p, a new Snf5p paralog, is essential for viability. The evolutionarily conserved domain of Sfh1p is sufficient for normal function, and Sfh1p interacts functionally and physically with an essential Snf2p paralog in a novel nucleosome-restructuring complex called RSC (for remodels the structure of chromatin). A temperature-sensitive sfh1 allele arrests cells in the G2/M phase of the cell cycle, and the Sfh1 protein is specifically phosphorylated in the G1 phase. Together, these results demonstrate a link between chromatin remodeling and progression through the cell division cycle, providing genetic clues to possible targets for RSC function.

scholarly journals The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1

2017 ◽  
Vol 114 (28) ◽  
pp. E5599-E5607 ◽  
Author(s):  
Fraser I. Young ◽  
Marc Keruzore ◽  
Xinsheng Nan ◽  
Nicole Gennet ◽  
Eric J. Bellefroid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Embryonic Stem ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Loss Of Function ◽  
Genomic Locus ◽  
Genome Wide ◽  
Conditional Mutant ◽  
Related Transcription Factor ◽  
Direct Binding

The mechanisms that determine whether a neural progenitor cell (NPC) reenters the cell cycle or exits and differentiates are pivotal for generating cells in the correct numbers and diverse types, and thus dictate proper brain development. Combining gain-of-function and loss-of-function approaches in an embryonic stem cell-derived cortical differentiation model, we report that doublesex- and mab-3–related transcription factor a2 (Dmrta2, also known as Dmrt5) plays an important role in maintaining NPCs in the cell cycle. Temporally controlled expression of transgenic Dmrta2 in NPCs suppresses differentiation without affecting their neurogenic competence. In contrast, Dmrta2 knockout accelerates the cell cycle exit and differentiation into postmitotic neurons of NPCs derived from embryonic stem cells and in Emx1-cre conditional mutant mice. Dmrta2 function is linked to the regulation of Hes1 and other proneural genes, as demonstrated by genome-wide RNA-seq and direct binding of Dmrta2 to the Hes1 genomic locus. Moreover, transient Hes1 expression rescues precocious neurogenesis in Dmrta2 knockout NPCs. Our study thus establishes a link between Dmrta2 modulation of Hes1 expression and the maintenance of NPCs during cortical development.

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