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Abstract：
Neurodevelopmental disorders are characterized by alterations in the development of the cerebral cortex, including aberrant changes in the number and function of neural cells. Although neurogenesis is one of the most studied cellular processes in these pathologies, little evidence is known about glial development. Genetic association studies have identified several genes associated with neurodevelopmental disorders. Indeed, variations in the PTPRD gene have been associated with numerous brain disorders, including autism spectrum disorder, restless leg syndrome, and schizophrenia. We previously demonstrated that constitutive loss of PTPRD expression induces significant alterations in cortical neurogenesis, promoting an increase in intermediate progenitors and neurons in mice. However, its role in gliogenesis has not been evaluated. To assess this, we developed a conditional knockout mouse model lacking PTPRD expression in telencephalon cells. Here, we found that the lack of PTPRD in the mouse cortex reduces glial precursors, astrocytes, and oligodendrocytes. According to our results, this decrease in gliogenesis resulted from a reduced number of radial glia cells at gliogenesis onset and a lower gliogenic potential in cortical neural precursors due to less activation of the JAK/STAT pathway and reduced expression of gliogenic genes. Our study shows PTPRD as a regulator of the glial/neuronal balance during cortical neurodevelopment and highlights the importance of studying glial development to understand the etiology of neurodevelopmental diseases.
摘要：
神经发育障碍的特征是大脑皮层发育的改变，包括神经细胞数量和功能的异常变化。尽管神经发生是这些病理中研究最多的细胞过程之一，关于神经胶质发育的证据很少。遗传关联研究已经确定了与神经发育障碍相关的几种基因。的确,PTPRD基因的变异与许多脑部疾病有关，包括自闭症谱系障碍,不宁腿综合征,和精神分裂症。我们以前证明，PTPRD表达的组成型缺失诱导皮质神经发生的显著改变，促进小鼠中间祖细胞和神经元的增加。然而,尚未评估其在胶质细胞生成中的作用。为了评估这一点，我们开发了一种在端脑细胞中缺乏PTPRD表达的条件性敲除小鼠模型。这里,我们发现小鼠皮质中缺乏PTPRD会减少神经胶质前体，星形胶质细胞,和少突胶质细胞。根据我们的结果,胶质细胞生成的这种减少是由于胶质细胞生成开始时放射状胶质细胞数量减少,以及由于JAK/STAT途径的激活减少和胶质细胞生成基因的表达减少,皮质神经前体的胶质细胞生成潜力降低.我们的研究表明PTPRD是皮质神经发育过程中神经胶质/神经元平衡的调节剂，并强调了研究神经胶质发育以了解神经发育疾病病因的重要性。
