Role of LGL1 in cerebellar primordium of embryonic mice.

IF 1.6 4区 医学 Q4 NEUROSCIENCES Neuroreport Pub Date : 2024-04-03 Epub Date: 2024-03-01 DOI:10.1097/WNR.0000000000002018
Congzhe Hou, Aizhen Zhang, Yecheng Jin, Chao Ye, Runze Li, Zhenhua Liu, Jiangang Gao
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Abstract

Lethal giant larvae 1 (LGL1) is originally recognized as a tumor suppressor, implicated in maintaining cell polarity in Drosophila and mammalian cells. Cell polarity plays a crucial role in tumorigenesis. We previously established Pax2-LGL1 -/- conditional knockout mice but did not focus on the tumorigenesis in cerebellar primordium. HE staining was used to detect the morphological structure of the cerebellar primordium during early embryonic development in Pax2-LGL1 -/- mice. Immunofluorescence assays were used to detect the expression of polar molecules. TUNEL staining assessed tissue apoptosis. Our findings reveal that deletion of LGL1 leads to the emergence of neuroblastoma-like tissues within the cerebellum primordium during early embryogenesis. This outcome can be attributed to alterations in expression patterns of polar molecules Cdc42 and β-catenin following early deletion of LGL1, resulting in loss of cell polarity among neuroepithelial cells and subsequent formation of tumor-like tissues. However, further histological examination demonstrated that these tumor-like tissues disappear from embryonic day 15.5 onwards within the cerebellar primordium of Pax2-LGL1 -/- mice due to apoptosis-mediated cellular compensation. Our data emphasize the importance of LGL1 in maintaining neuroepithelial cell polarity and reveal a novel role for LGL1 in regulating tumorigenesis and ablation in the cerebellar primordium.

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LGL1 在胚胎小鼠小脑原基中的作用
致命巨幼虫 1(LGL1)最初被认为是一种肿瘤抑制因子,与果蝇和哺乳动物细胞中细胞极性的维持有关。细胞极性在肿瘤发生中起着至关重要的作用。我们以前曾建立过 Pax2-LGL1-/- 条件性基因敲除小鼠,但没有关注小脑原基的肿瘤发生。我们用HE染色法检测了Pax2-LGL1-/-小鼠在胚胎早期发育过程中小脑初级体的形态结构。免疫荧光试验用于检测极性分子的表达。TUNEL染色评估组织凋亡。我们的研究结果表明,在胚胎早期发育过程中,LGL1的缺失会导致小脑基底出现神经母细胞瘤样组织。这一结果可归因于LGL1早期缺失后极性分子Cdc42和β-catenin的表达模式发生了改变,导致神经上皮细胞间失去细胞极性,进而形成瘤样组织。然而,进一步的组织学检查表明,由于细胞凋亡介导的细胞代偿,这些瘤样组织从胚胎第15.5天起就在Pax2-LGL1-/小鼠的小脑原基中消失了。我们的数据强调了LGL1在维持神经上皮细胞极性中的重要性,并揭示了LGL1在调节小脑基底层肿瘤发生和消融中的新作用。
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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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