DEVELOPMENTAL CELL
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2023
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IF 11.8
Xue-Lian Sun,Zhen-Hua Chen,Xize Guo,Jingjing Wang,Mengmeng Ge,Samuel Zheng Hao Wong,Ting Wang,Si Li,Mingze Yao,Laura A. Johnston,Qing-Feng Wu
Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.
研究领域:
神经科学
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发育生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF VIROLOGY
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2018
·Vol. 92
·期 17
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IF 4.368
Cong-Cong Wu,Xuan Jiang,Xian-Zhang Wang,Xi-Juan Liu,Xiao-Jun Li,Bo Yang,Han-Qing Ye,Thomas Harwardt,Man Jiang,Hui-Min Xia,Wei Wang,William J. Britt,Christina Paulus,Michael Nevels,Min-Hua Luo
The mechanisms underlying neurodevelopmental damage caused by virus infections remain poorly defined. Congenital human cytomegalovirus (HCMV) infection is the leading cause of fetal brain development disorders. Previous work has linked HCMV infection to perturbations of neural cell fate, including premature differentiation of neural progenitor cells (NPCs). Here, we show that HCMV infection of NPCs results in loss of the SOX2 protein, a key pluripotency-associated transcription factor. SOX2 depletion maps to the HCMV major immediate early (IE) transcription unit and is individually mediated by the IE1 and IE2 proteins. IE1 causes SOX2 downregulation by promoting the nuclear accumulation and inhibiting the phosphorylation of STAT3, a transcriptional activator of SOX2 expression. Deranged signaling resulting in depletion of a critical stem cell protein is an unanticipated mechanism by which the viral major IE proteins may contribute to brain development disorders caused by congenital HCMV infection.IMPORTANCE Human cytomegalovirus (HCMV) infections are a leading cause of brain damage, hearing loss, and other neurological disabilities in children. We report that the HCMV proteins known as IE1 and IE2 target expression of human SOX2, a central pluripotency-associated transcription factor that governs neural progenitor cell (NPC) fate and is required for normal brain development. Both during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream regulator of SOX2 expression. Our findings reveal an unanticipated mechanism by which a common virus may cause damage to the developing nervous system and suggest novel targets for medical intervention.
研究领域:
病毒学
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神经科学
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发育生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL
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2025
·
IF 42.5
Zhen Long,Yongzhen Yu,Chenyi He,Linhe Xu,Yiming Yan,Zhuoru Li,Zengcai V. Guo,Da Mi
The mammalian brain contains diverse neuronal and immune cell types that exhibit dynamic motions in response to distinct extracellular environments. However, technical limitations make it difficult to investigate complex cellular motions in the developing brain in vivo . Here, we establish the intravital imaging of externally immobilized embryos (IMEE) method for long-term, large-field, and deep-depth imaging of mouse embryos, excelling in viewing angle flexibility, procedural simplicity, and functional applicability. Through combining IMEE with in utero retro-orbital injection and topological analysis of vector fields, we characterize distinct neuronal migration patterns and illustrate interactions among neurons, immune cells, and vasculature under physiological conditions and environmental stress during brain development. Our results suggest that neuronal migration guidance and immune surveillance depend on cellular adaptation to the local environment through distinct motion patterns of somata or processes. Our findings provide critical insight into the environmentally adaptive nature of neural cells in the developmental landscape.
研究领域:
神经科学
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发育生物学
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免疫学
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活体成像
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2021
·
IF 9.028
Yuxuan Liu,Yonghua Wang,Xin Ling,Zhenhua Yan,Donghai Wu,Jianchao Liu,Guanghua Lu
Nanoplastics with small particle sizes and high surface area/volume ratios easily absorb environmental pollutants and affect their bioavailability. In this study, polystyrene nanoplastic beads (PS-NPBs) with a particle size of 100 nm and butyl methoxydibenzoylmethane (BMDBM) sunscreen in personal-care products were chosen as target pollutants to study their developmental toxicity and interactive effects on zebrafish embryos. The exposure period was set from 2 to 12 h postfertilization (hpf). BMDBM and PS-NPBs significantly upregulated genes related to antioxidant enzymes and downregulated the gene expression of aromatase and DNA methyltransferases, but the influenced genes were not exactly the same. The combined exposure reduced the adverse effects on the expression of all genes. With the help of the single-cell RNA sequencing technology, neural mid cells were identified as the target cells of both pollutants, and brain development, head development, and the notch signaling pathway were the functions they commonly altered. The key genes and functions that are specifically affected by BMDBM and/or PS-NPBs were identified. BMDBM mainly affects the differentiation and fate of neurons in the central nervous system through the regulation of her5, her6, her11, lfng, pax2a, and fgfr4. The PS-NPBs regulate the expression of olig2, foxg1a, fzd8b, six3a, rx1, lhx2b, nkx2.1a, and sfrp5 to alter nervous system development, retinal development, and stem cell differentiation. The phenotypic responses of zebrafish larvae at 120 hpf were tested, and significant inhibition of locomotor activity was found, indicating that early effects on the central nervous system would have a sustained impact on the behavior of zebrafish.
研究领域:
毒理学
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发育生物学
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分子生物学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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