The 11th International Symposium on 3D Genomics

85 / 2024-10-20 21:00:48

Molecular Mechanism of CTCF Regulating Astrocyte Localization in Cortical Excitatory Neurons

CTCF; communication; localization; Corpus Callosum;

CTCF, as a highly conserved nuclear protein commonly expressed in eukaryotes, is essential for maintaining higher chromatin structure to regulate gene expression. The specific knockout of Ctcf in different cell lines has revealed that it plays a key role in different cell groups, but the in vivo function of CTCF in the nervous system remains to be explored. In our study, we found that CTCF expression in cortex, hippocampus and striatum was significantly reduced in mice with Ctcf -specific knockout of excitatory neurons, and GFAP-positive cells in cortex showed significant localization abnormalities. Compared with control mice, Ctcf -cKO mice showed a significant increase in the number of GFAP+ cells in the deeper cortical layers (SS5 SS6), a decrease at the corpus callosum (CC), and no significant difference in the superficial cortical layers (I-IV), with an overall tendency to spread from the corpus callosum to the deeper cortical layers (layers V / VI). RNA-seq of neurons and astrocytes after FACS and MACS sorting revealed that pathways related to signaling were enriched in both cell type, suggesting that cellular communication between neuron and astrocyte was disturbed. These results suggest that CTCF in cortical excitatory neurons may interfere with the proper localization of astrocytes by regulating the expression of key molecules that mediate signaling between neurons and astrocytes, thereby impeding the development and formation of the corpus callosum.