Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany.
German Center for Neurodegenerative Diseases, Goettingen, Germany.
Stem Cell Reports. 2021 Apr 13;16(4):968-984. doi: 10.1016/j.stemcr.2021.03.008. Epub 2021 Apr 1.
Intermediate progenitor cells (IPCs) are neocortical neuronal precursors. Although IPCs play crucial roles in corticogenesis, their molecular features remain largely unknown. In this study, we aimed to characterize the molecular profile of IPCs. We isolated TBR2-positive (+) IPCs and TBR2-negative (-) cell populations in the developing mouse cortex. Comparative genome-wide gene expression analysis of TBR2 IPCs versus TBR2 cells revealed differences in key factors involved in chromatid segregation, cell-cycle regulation, transcriptional regulation, and cell signaling. Notably, mutation of many IPC genes in human has led to intellectual disability and caused a wide range of cortical malformations, including microcephaly and agenesis of corpus callosum. Loss-of-function experiments in cortex-specific mutants of Esco2, one of the novel IPC genes, demonstrate its critical role in IPC maintenance, and substantiate the identification of a central genetic determinant of IPC biogenesis. Our data provide novel molecular characteristics of IPCs in the developing mouse cortex.
中间祖细胞 (IPC) 是皮质神经元的前体细胞。尽管 IPC 在皮质发生中起着至关重要的作用，但它们的分子特征在很大程度上仍然未知。在这项研究中，我们旨在表征 IPC 的分子特征。我们在发育中的小鼠皮质中分离出 TBR2 阳性 (+) IPC 和 TBR2 阴性 (-) 细胞群。TBR2 IPC 与 TBR2 细胞的全基因组基因表达比较分析显示，参与染色单体分离、细胞周期调控、转录调控和细胞信号转导的关键因子存在差异。值得注意的是，人类许多 IPC 基因的突变导致智力残疾，并导致广泛的皮质畸形，包括小头畸形和胼胝体发育不全。Esco2（一种新的 IPC 基因之一）在皮质特异性突变体中的功能丧失实验表明其在 IPC 维持中的关键作用，并证实了 IPC 发生的中央遗传决定因素的鉴定。我们的数据提供了发育中的小鼠皮质中 IPC 的新分子特征。
