Molecular Profiling Reveals Involvement of ESCO2 in Intermediate Progenitor Cell Maintenance in the Developing Mouse Cortex.
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, Andre Fischer, Gregor Eichele, Jochen F Staiger, Tran Tuoc
Author Information
Pauline Antonie Ulmke: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany.
M Sadman Sakib: German Center for Neurodegenerative Diseases, Goettingen, Germany.
Peter Ditte: Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
Godwin Sokpor: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany; Department of Human Genetics, Ruhr University of Bochum, Bochum, Germany.
Cemil Kerimoglu: German Center for Neurodegenerative Diseases, Goettingen, Germany.
Linh Pham: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany; Department of Human Genetics, Ruhr University of Bochum, Bochum, Germany.
Yuanbin Xie: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany.
Xiaoyi Mao: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany.
Joachim Rosenbusch: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany.
Ulrike Teichmann: Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
Huu Phuc Nguyen: Department of Human Genetics, Ruhr University of Bochum, Bochum, Germany.
Andre Fischer: German Center for Neurodegenerative Diseases, Goettingen, Germany; Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), Goettingen, Germany.
Gregor Eichele: Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
Jochen F Staiger: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany.
Tran Tuoc: Institute for Neuroanatomy, University Medical Center, Georg-August-University, Goettingen, Germany; Department of Human Genetics, Ruhr University of Bochum, Bochum, Germany. Electronic address: tran.tuoc@ruhr-uni-bochum.de.
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.
