C-Terminal Binding Proteins Promote Neurogenesis and Oligodendrogenesis in the Subventricular Zone

Catarina Serra-Almeida; Cláudia Saraiva; Marta Esteves; Raquel Ferreira; Tiago Santos; Ana Clara Cristóvão; Liliana Bernardino

doi:10.3389/fcell.2020.584220

C-Terminal Binding Proteins Promote Neurogenesis and Oligodendrogenesis in the Subventricular Zone

Front Cell Dev Biol. 2021 Jan 6:8:584220. doi: 10.3389/fcell.2020.584220. eCollection 2020.

Authors

Catarina Serra-Almeida¹, Cláudia Saraiva¹, Marta Esteves¹, Raquel Ferreira¹, Tiago Santos¹, Ana Clara Cristóvão^{1

2}, Liliana Bernardino¹

Affiliations

¹ Faculty of Health Sciences, Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Covilhã, Portugal.
² NeuroSoV, UBImedical, University of Beira Interior, Covilhã, Portugal.

Abstract

C-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet. Herein, we evaluate the expression and functions of CtBPs in postnatal NSCs from the subventricular zone (SVZ). We found that CtBPs were expressed in immature/progenitor cells, neurons and glial cells in the SVZ niche. Using the CtBPs modulator 4-methylthio 2-oxobutyric acid (MTOB), our results showed that 1 mM of MTOB induced cell death, while 5, 25, and 50 μM increased the number of proliferating neuroblasts, mature neurons, and oligodendrocytes. Interestingly, it also increased the dendritic complexity of immature neurons. Altogether, our results highlight CtBPs putative application for brain regenerative applications.

Keywords: C-terminal binding proteins; neural stem cells; neurogenesis; oligodendrogenesis; subventricular zone.