The Tbr2 Molecular Network Controls Cortical Neuronal Differentiation Through Complementary Genetic and Epigenetic Pathways

A Sessa, Ernesto Ciabatti, D Drechsel, L Massimino, G Colasante, S Giannelli, T Satoh, S Akira, F Guillemot, V Broccoli

Research output: Contribution to journalArticlepeer-review

Abstract

The T-box containing Tbr2 gene encodes for a transcription factor essential for the specification of the intermediate neural progenitors (INPs) originating the excitatory neurons of the cerebral cortex. However, its overall mechanism of action, direct target genes and cofactors remain unknown. Herein, we carried out global gene expression profiling combined with genome-wide binding site identification to determine the molecular pathways regulated by TBR2 in INPs. This analysis led to the identification of novel protein-protein interactions that control multiple features of INPs including cell-type identity, morphology, proliferation and migration dynamics. In particular, NEUROG2 and JMJD3 were found to associate with TBR2 revealing unexplored TBR2-dependent mechanisms. These interactions can explain, at least in part, the role of this transcription factor in the implementation of the molecular program controlling developmental milestones during corticogenesis. These data identify TBR2 as a major determinant of the INP-specific traits by regulating both genetic and epigenetic pathways. © The Author 2016. Published by Oxford University Press.
Original languageEnglish
Pages (from-to)3378-3396
Number of pages19
JournalCerebral Cortex
Volume27
Issue number6
DOIs
Publication statusPublished - 2017

Fingerprint Dive into the research topics of 'The Tbr2 Molecular Network Controls Cortical Neuronal Differentiation Through Complementary Genetic and Epigenetic Pathways'. Together they form a unique fingerprint.

Cite this