2023 72 B3

Investigating the Role of SETD2 in Cell Fate Specification in the Developing Cortex

By: Gloria Anyanwu

Department: Biology

Faculty Advisor: Dr. Lily Chen

SETD2 is the lysine-36 of histone H3 trimethyltransferase (H3K36me3). SETD2 is involved in several biological processes including transcriptional regulation, alternative RNA splicing, and cellular mechanisms during embryogenesis and carcinogenesis. Targeted deletion of SETD2 in the developing cortex eliminates H3K36me3 from both neural stem cells and their progeny. The absence of H3K36me3 activity negatively affects alternative splicing and introduces defects in cortical area patterning, particularly in the upper-layer region of the cerebral cortex. Preliminary data from the Harwell lab at UCSF shows hemorrhaging and subsequent phenotypic degeneration of the cerebral cortex, mostly in the motor cortex (M1/M2) in homozygous SETD2 KO mice. Moreover, a reduction in gliogenic progenitor cells was observed. It is unclear whether the lost glial progenitor cells are astrocytes, oligodendrocytes, or both. The visual cortex appears to be unaffected by the SETD2 knockout. The visual cortex is used as a comparison to the affected motor cortex to assess phenotypic variability in different regions of the brain.