Molecular Neurobiology ( IF 4.6 ) Pub Date : 2024-01-19 , DOI: 10.1007/s12035-024-03943-w
Jemma G Gasperoni 1 , Stephanie C Tran 1 , Sylvia V H Grommen 1, 2 , Bert De Groef 1, 2 , Sebastian Dworkin 1
|
The pleomorphic adenoma gene 1 (Plag1) is a transcription factor involved in the regulation of growth and cellular proliferation. Here, we report the spatial distribution and functional implications of PLAG1 expression in the adult mouse brain. We identified Plag1 promoter-dependent β-galactosidase expression in various brain structures, including the hippocampus, cortex, choroid plexus, subcommisural organ, ependymal cells lining the third ventricle, medial and lateral habenulae and amygdala. We noted striking spatial-restriction of PLAG1 within the cornu ammonis (CA1) region of the hippocampus and layer-specific cortical expression, with abundant expression noted in all layers except layer 5. Furthermore, our study delved into the role of PLAG1 in neurodevelopment, focusing on its impact on neural stem/progenitor cell proliferation. Loss of Plag1 resulted in reduced proliferation and decreased production of neocortical progenitors in vivo, although ex vivo neurosphere experiments revealed no cell-intrinsic defects in the proliferative or neurogenic capacity of Plag1-deficient neural progenitors. Lastly, we explored potential target genes of PLAG1 in the cortex, identifying that Neurogenin 2 (Ngn2) was significantly downregulated in Plag1-deficient mice. In summary, our study provides novel insights into the spatial distribution of PLAG1 expression in the adult mouse brain and its potential role in neurodevelopment. These findings expand our understanding of the functional significance of PLAG1 within the brain, with potential implications for neurodevelopmental disorders and therapeutic interventions.
中文翻译:

PLAG1 在小鼠大脑发育和神经发生中的作用
多形性腺瘤基因 1 ( Plag1 ) 是一种参与生长和细胞增殖调节的转录因子。在这里,我们报告了成年小鼠大脑中 PLAG1 表达的空间分布和功能意义。我们在各种脑结构中发现了 Plag1 启动子依赖性 β-半乳糖苷酶的表达,包括海马、皮质、脉络丛、连合下器官、第三脑室内衬的室管膜细胞、内侧和外侧缰核和杏仁核。我们注意到 PLAG1 在海马角 (CA1) 区域和层特异性皮质表达中存在显着的空间限制,在除第 5 层之外的所有层中都有丰富的表达。此外,我们的研究深入研究了 PLAG1 在神经发育中的作用,重点关注其对神经干/祖细胞增殖的影响。尽管离体神经球实验显示Plag1缺陷的神经祖细胞的增殖或神经发生能力没有细胞内在缺陷,但Plag1的缺失导致体内新皮质祖细胞的增殖减少和产生减少。最后,我们探索了皮质中 PLAG1 的潜在靶基因,发现 Neurogenin 2 ( Ngn2 ) 在 Plag1 缺陷小鼠中显着下调。总之,我们的研究为成年小鼠大脑中 PLAG1 表达的空间分布及其在神经发育中的潜在作用提供了新的见解。这些发现扩展了我们对 PLAG1 在大脑中的功能意义的理解,对神经发育障碍和治疗干预具有潜在影响。