Mancinelli Sara, Vitiello Michela, Donnini Maria, Mantile Francesca, Palma Giuseppe, Luciano Antonio, Arra Claudio, Cerchia Laura, Liguori Giovanna Lucia, Fedele Monica
Institute of Genetics and Biophysics, National Research Council, Naples, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
Front Cell Dev Biol. 2021 Apr 7;9:657149. doi: 10.3389/fcell.2021.657149. eCollection 2021.
Proper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator is ubiquitously expressed in early mouse embryos and has a key role in embryonic stem cell maintenance. At later stages, the detection of expression mainly in the developing brain suggests a specific involvement of in neurogenesis. To address this point, we first got insights in expression profile in different brain territories at both embryonic and postnatal stages, evidencing a general decreasing trend with respect to time. Then, we performed and analysis of -knockout mice, focusing on the ventricular and subventricular zone, where we confirmed enrichment through the analysis of public RNA-seq datasets. Both embryos and adults showed a significant reduction in the number of -null NS/PCs, as well as of their self-renewal capability, compared to controls. Consistently, molecular analysis revealed the downregulation of stemness markers in NS/PCs derived from -null mice. Overall, these data demonstrate the requirement of Patz1 for NS/PC maintenance and proliferation, suggesting new roles for this key transcription factor specifically in brain development and plasticity, with possible implications for neurodegenerative disorders and glial brain tumors.
神经发生是指神经干细胞和祖细胞（NS/PCs）产生新神经元的过程，对胚胎脑发育和成年脑功能至关重要。转录调节因子在小鼠早期胚胎中普遍表达，在胚胎干细胞维持中起关键作用。在后期阶段，检测到其表达主要在发育中的大脑中，这表明其在神经发生中具有特定作用。为了解决这一问题，我们首先深入了解了其在胚胎期和出生后不同脑区的表达谱，发现其表达随时间总体呈下降趋势。然后，我们对Patz1基因敲除小鼠进行了RNA测序和蛋白质印迹分析，重点关注脑室和室下区，通过分析公共RNA测序数据集证实了Patz1在这些区域的富集。与对照组相比，胚胎和成年小鼠中Patz1基因缺失的NS/PCs数量以及它们的自我更新能力均显著减少。一致地，分子分析显示来自Patz1基因缺失小鼠的NS/PCs中干性标记物下调。总体而言，这些数据证明了Patz1对NS/PC维持和增殖的必要性，表明这个关键转录因子在脑发育和可塑性中具有新作用，可能对神经退行性疾病和胶质脑瘤有影响。
