Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex

ABSTRACT: Neural stem cells (NSCs) can give rise to both neurons and glia, but the regulatory mechanisms governing their differentiation transitions remain incompletely understood. Here, we address the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stages of dorsal cortical development. We find that the CDKIs p18 and p27 are upregulated at the onset of astrocyte generation. Acute manipulation of p18 and p27 levels shows that CDKIs modulate lineage switching between upper-layer neurons and astrocytes at the transitional stage. We generate a conditional knock-in mouse model to induce p18 in NSCs. The transcriptomic deconvolution of microdissected tissue reveals that increased levels of p18 promote glial cell development and activate Delta-Notch signaling. Furthermore, we show that p18

SUBMITTER: Prof. Yoichi Kosodo 

PROVIDER: S-SCDT-10_1038-S44318-024-00325-9 | biostudies-other |

REPOSITORIES: biostudies-other