Molecular Profiling Reveals Involvement of ESCO2 in Intermediate Progenitor Cell Maintenance in the Developing Mouse Cortex

作者：Pauline Antonie Ulmke, M. Sadman Sakib, Peter Ditte, Godwin Sokpor, Cemil Kerimoglu, Linh Pham, Yuanbin Xie, Xiaoyi Mao, Joachim Rosenbusch, Ulrike Teichmann, Huu Phuc Nguyen, André Fischer, Gregor Eichele, Jochen F. Staiger, Tran Tuoc · 发表于：Stem Cell Reports · 年份：2021 · DOI：10.1016/j.stemcr.2021.03.008 · 被引用次数：10 · 研究领域：Epigenetics and DNA Methylation、Neurogenesis and neuroplasticity mechanisms、Genetics and Neurodevelopmental Disorders

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.