p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53

The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.

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Transcriptome Analysis Identifies SenZfp536, a Sense LncRNA that Suppresses Self-renewal of Cortical Neural Progenitors

Neuroscience Bulletin ◽

10.1007/s12264-020-00607-2 ◽

2020 ◽

Author(s):

Kuan Tian ◽

Andi Wang ◽

Junbao Wang ◽

Wei Li ◽

Wenchen Shen ◽

...

Keyword(s):

Transcriptome Analysis ◽

Neural Progenitors ◽

Self Renewal

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Stabilized β-Catenin Functions through TCF/LEF Proteins and the Notch/RBP-Jκ Complex To Promote Proliferation and Suppress Differentiation of Neural Precursor Cells

Molecular and Cellular Biology ◽

10.1128/mcb.01962-07 ◽

2008 ◽

Vol 28 (24) ◽

pp. 7427-7441 ◽

Cited By ~ 122

Author(s):

Takeshi Shimizu ◽

Tetsushi Kagawa ◽

Toshihiro Inoue ◽

Aya Nonaka ◽

Shinji Takada ◽

...

Keyword(s):

Cell Proliferation ◽

Neuronal Differentiation ◽

Glycogen Synthase ◽

Precursor Cells ◽

Precursor Cell ◽

Neural Precursor Cells ◽

Neural Precursor ◽

Self Renewal ◽

Fgf Receptor ◽

Proliferation And Differentiation

ABSTRACT The proliferation and differentiation of neural precursor cells are mutually exclusive during brain development. Despite its importance for precursor cell self renewal, the molecular linkage between these two events has remained unclear. Fibroblast growth factor 2 (FGF2) promotes neural precursor cell proliferation and concurrently inhibits their differentiation, suggesting a cross talk between proliferation and differentiation signaling pathways downstream of the FGF receptor. We demonstrate that FGF2 signaling through phosphatidylinositol 3 kinase activation inactivates glycogen synthase kinase 3β (GSK3β) and leads to the accumulation of β-catenin in a manner different from that in the Wnt canonical pathway. The nuclear accumulated β-catenin leads to cell proliferation by activating LEF/TCF transcription factors and concurrently inhibits neuronal differentiation by potentiating the Notch1-RBP-Jκ signaling pathway. β-Catenin and the Notch1 intracellular domain form a molecular complex with the promoter region of the antineurogenic hes1 gene, allowing its expression. This signaling interplay is especially essential for neural stem cell maintenance, since the misexpression of dominant-active GSK3β completely inhibits the self renewal of neurosphere-forming stem cells and prompts their neuronal differentiation. Thus, the GSK3β/β-catenin signaling axis regulated by FGF and Wnt signals plays a pivotal role in the maintenance of neural stem/precursor cells by linking the cell proliferation to the inhibition of differentiation.

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Structural Basis for Self-Renewal of Neural Progenitors in Cortical Neurogenesis

Cerebral Cortex ◽

10.1093/cercor/bhp042 ◽

2009 ◽

Vol 19 (suppl 1) ◽

pp. i55-i61 ◽

Cited By ~ 14

Author(s):

G. Shioi ◽

D. Konno ◽

A. Shitamukai ◽

F. Matsuzaki

Keyword(s):

Neural Progenitors ◽

Structural Basis ◽

Self Renewal ◽

Cortical Neurogenesis

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Enhanced viability and neuronal differentiation of neural progenitors by chromaffin cell co-culture

Developmental Brain Research ◽

10.1016/s0165-3806(02)00415-7 ◽

2002 ◽

Vol 137 (2) ◽

pp. 115-125 ◽

Cited By ~ 14

Author(s):

Michael A Schumm ◽

Daniel A Castellanos ◽

Beata R Frydel ◽

Jacqueline Sagen

Keyword(s):

Neuronal Differentiation ◽

Chromaffin Cell ◽

Neural Progenitors

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Anti-aging effects exerted by Tetramethylpyrazine enhances self-renewal and neuronal differentiation of rat bMSCs by suppressing NF-kB signaling

Bioscience Reports ◽

10.1042/bsr20190761 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 3

Author(s):

Xiaoqing Song ◽

Jin Dai ◽

Huaguang Li ◽

Yuemeng Li ◽

Weixiao Hao ◽

...

Keyword(s):

Neuronal Differentiation ◽

Neuron Specific Enolase ◽

Neuronal Morphology ◽

Biologically Active ◽

Therapeutic Effects ◽

Aging Effects ◽

Neuroprotective Effects ◽

Self Renewal ◽

Neuronal Markers ◽

Wide Range

AbstractIn order to improve the therapeutic effects of mesenchymal stem cell (MSC)-based therapies for a number of intractable neurological disorders, a more favorable strategy to regulate the outcome of bone marrow MSCs (bMSCs) was examined in the present study. In view of the wide range of neurotrophic and neuroprotective effects, Tetramethylpyrazine (TMP), a biologically active alkaloid isolated from the herbal medicine Ligusticum wallichii, was used. It was revealed that treatment with 30–50 mg/l TMP for 4 days significantly increased cell viability, alleviated senescence by suppressing NF-κB signaling, and promoted bMSC proliferation by regulating the cell cycle. In addition, 40–50 mg/l TMP treatment may facilitate the neuronal differentiation of bMSCs, verified in the present study by presentation of neuronal morphology and expression of neuronal markers: microtubule-associated protein 2 (MAP-2) and neuron-specific enolase (NSE). The quantitative real-time polymerase chain reaction (qRT-PCR) revealed that TMP treatment may promote the expression of neurogenin 1 (Ngn1), neuronal differentiation 1 (NeuroD) and mammalian achaete–scute homolog 1 (Mash1). In conclusion, 4 days of 40–50 mg/l TMP treatment may significantly delay bMSC senescence by suppressing NF-κB signaling, and enhancing the self-renewal ability of bMSCs, and their potential for neuronal differentiation.

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