Journal Article

DZNE-2021-01209

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular Profiling Reveals Involvement of ESCO2 in Intermediate Progenitor Cell Maintenance in the Developing Mouse Cortex.

Ulmke, P. A. ; Sakib, M. S.DZNE* ; Ditte, P. ; Sokpor, G. ; Kerimoglu, C.DZNE* ; Pham, L. ; Xie, Y. ; Mao, X. ; Rosenbusch, J. ; Teichmann, U. ; Nguyen, H. P. ; Fischer, A.DZNE* ; Eichele, G. ; Staiger, J. F. ; Tuoc, T.

2021
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.stemcr.2021.03.008

Abstract: 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.

Keyword(s): Acetyltransferases: genetics (MeSH) ; Acetyltransferases: metabolism (MeSH) ; Animals (MeSH) ; Apoptosis: genetics (MeSH) ; Cerebral Cortex: cytology (MeSH) ; Cerebral Cortex: embryology (MeSH) ; Chromatids: metabolism (MeSH) ; Chromosome Segregation: genetics (MeSH) ; Gene Expression Profiling (MeSH) ; Gene Expression Regulation (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Mitosis: genetics (MeSH) ; Mutation: genetics (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Neural Stem Cells: metabolism (MeSH) ; Neurodevelopmental Disorders: genetics (MeSH) ; Neurodevelopmental Disorders: pathology (MeSH) ; Signal Transduction (MeSH) ; ESCO2 ; TBR2 ; apoptosis ; cell-cycle regulation ; chromosome segregation ; cortical development ; cortical malformation ; intermediate progenitor cells ; signaling pathways ; transcription factors ; transcriptome

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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