ePoster

C-terminal binding protein 1 is necessary for normal migration of adult-born neurons

Burcu Sucu, Neeraja Suresh, Lena Marx, Enes Yağız Akdaş, Bartomeu Perelló-Amorós, Renato Frischknecht, Anna Fejtová
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Burcu Sucu, Neeraja Suresh, Lena Marx, Enes Yağız Akdaş, Bartomeu Perelló-Amorós, Renato Frischknecht, Anna Fejtová

Abstract

The C-terminal binding protein 1 (CtBP1) is a ubiquitously expressed, dual-function protein. In the nucleus, it nucleates corepressor complexes that control chromatin-modification and gene expression. In the cytoplasm, it regulates membrane trafficking processes by controlling the membrane fission reaction. Our previous study revealed an involvement of CtBP1 in the control of neural activity‐regulated genes such as BDNF, Arc and Fos in the mature brain. Recently, individuals with a missense mutation in CTBP1 have been reported to have intellectual disability and neurodevelopmental problems. The CtBP protein family has been proposed to regulate neuronal and glial differentiation. However, the role of CtBP1 in neurodevelopmental processes is still underexplored. Here, we investigated adult hippocampal neurogenesis in constitutive CtBP1 knock-out animals. Using BrdU pulse-chase experiments, we found a dramatic decrease in the number of newly generated mature and immature neurons. These data suggest that the absence of CtBP1 impairs differentiation of neural stem/progenitor cells (NSPCs) in adult hippocampus. To identify CtBP1-dependent expressional networks important for adult neurogenesis, we performed bulk RNA sequencing on neural progenitor cells (NPCs) that were derived from the hippocampal subgranular zone of constitutive CtBP1 knock-out and wild-type mice, and cultured in vitro. We identified 31 significantly differentially expressed genes. GO analysis of these genes revealed significant enrichment for biological processes including neuroblast proliferation, migration and differentiation, as well as, cell adhesion and histone modifications. Our findings highlight the importance of CtBP1 in the differentiation and maturation of newly born neurons, likely by impacting their migration and adhesion capabilities.

Unique ID: fens-24/c-terminal-binding-protein-necessary-79e55264