Chromatin Remodeling BAF155 Subunit Regulates the Genesis of Basal Progenitors in Developing Cortex

Ramanathan Narayanan; Linh Pham; Cemil Kerimoglu; Takashi Watanabe; Ricardo Castro Hernandez; Godwin Sokpor; Pauline Antonie Ulmke; Kamila A Kiszka; Anton B Tonchev; Joachim Rosenbusch; Rho H Seong; Ulrike Teichmann; Jens Frahm; Andre Fischer; Stefan Bonn; Anastassia Stoykova; Jochen F Staiger; Tran Tuoc

doi:10.1016/j.isci.2018.05.014

Chromatin Remodeling BAF155 Subunit Regulates the Genesis of Basal Progenitors in Developing Cortex

iScience. 2018 Jun 29:4:109-126. doi: 10.1016/j.isci.2018.05.014. Epub 2018 May 23.

Authors

Ramanathan Narayanan¹, Linh Pham¹, Cemil Kerimoglu², Takashi Watanabe³, Ricardo Castro Hernandez¹, Godwin Sokpor¹, Pauline Antonie Ulmke¹, Kamila A Kiszka⁴, Anton B Tonchev⁵, Joachim Rosenbusch¹, Rho H Seong⁶, Ulrike Teichmann³, Jens Frahm³, Andre Fischer⁷, Stefan Bonn², Anastassia Stoykova⁸, Jochen F Staiger⁴, Tran Tuoc⁹

Affiliations

¹ Institute of Neuroanatomy, University Medical Center, Georg-August-University, 37075 Goettingen, Germany.
² German Center for Neurodegenerative Diseases, 37075 Goettingen, Germany.
³ Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
⁴ Institute of Neuroanatomy, University Medical Center, Georg-August-University, 37075 Goettingen, Germany; DFG, Center for Molecular Physiology of the Brain (CMPB), 37075 Goettingen, Germany.
⁵ Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany; Department of Anatomy and Cell Biology, Medical University-Varna, BG-9002 Varna, Bulgaria.
⁶ Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea.
⁷ German Center for Neurodegenerative Diseases, 37075 Goettingen, Germany; DFG, Center for Molecular Physiology of the Brain (CMPB), 37075 Goettingen, Germany.
⁸ Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany; DFG, Center for Molecular Physiology of the Brain (CMPB), 37075 Goettingen, Germany. Electronic address: astoyko@gwdg.de.
⁹ Institute of Neuroanatomy, University Medical Center, Georg-August-University, 37075 Goettingen, Germany; DFG, Center for Molecular Physiology of the Brain (CMPB), 37075 Goettingen, Germany. Electronic address: tran.tuoc@med.uni-goettingen.de.

Abstract

The abundance of basal progenitors (BPs), basal radial glia progenitors (bRGs) and basal intermediate progenitors (bIPs), in primate brain has been correlated to the high degree of cortical folding. Here we examined the role of BAF155, a subunit of the chromatin remodeling BAF complex, in generation of cortical progenitor heterogeneity. The conditional deletion of BAF155 led to diminished bIP pool and increased number of bRGs, due to delamination of apical RGs. We found that BAF155 is required for normal activity of neurogenic transcription factor PAX6, thus controlling the expression of genes that are involved in bIP specification, cell-cell interaction, and establishment of adherens junction. In a PAX6-dependent manner, BAF155 regulates the expression of the CDC42 effector protein CEP4, thereby controlling progenitor delamination. Furthermore, BAF155-dependent chromatin remodeling seems to exert a specific role in the genesis of BPs through the regulation of human RG-specific genes (such as Foxn4) that possibly acquired evolutionary significance.

Keywords: Developmental Neuroscience; Molecular Neuroscience; Neuroscience.