Characterization of Histone Methylation gene Ktm2a in Cortical Specificity and Connectivity – UROP Spring Symposium 2022

Characterization of Histone Methylation gene Ktm2a in Cortical Specificity and Connectivity

photo of presenter

Jeremy Nelson

Pronouns: he/him

Research Mentor(s): Kenneth Kwan
Co-Presenter:
Research Mentor School/College/Department: Michigan Neuroscience Institute / Human Genetics / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 5 – 3:40pm – 4:30 pm
Room: League Ballroom
Authors: Daniel Z. Doyle, Jeremy Nelson, Mandy Lam, Kenneth Kwan
Presenter: 51

Abstract

The cerebral cortex is the outer layer of the brain, serving a number of important functions carried out through complex and diverse neural networks. Each neuron requires specific gene expressions in order to have the proper identity and function. Gene expression relies on DNA organization in order to efficiently and accurately read the DNA. DNA is organized around histones, which can have a multitude of posttranslational modifications (PTMs) that influence accessibility of genes. Specialized proteins regulate the localization of the PTMs. The KMT2A protein acts to regulate methylation on the histone H3 lysine 4 (H3K4) and is especially important during development. Mutations in Kmt2a are associated with Autism Spectrum Disorder and neurodevelopmental disorder Wiedmann-Steiner syndrome. We used antibody staining and conditional mouse genetics to study the development of the cortex in control mice and mice with Kmt2a deleted specifically from postmitotic excitatory neurons of the cortex using Neurod6Cre. We used immunohistochemistry to study the sensory whisker barrels in both the control (ctrl) and conditional knockout (cKO) brains. We found that the ctrl mice had a stereotyped pattern of barrels, however the cKO mice showed disrupted formation in their barrels. Along with the loss of whisker barrels, we noticed a reduction in upper-layer cortical neurons (layers 2-4) in the cKO as well as the aberrant localization of upper-layer neurons into the deep layers (layer 5 & 6). While previous work suggests that such an effect may exist, there has been no exploration into the specific effects on the cortex. Our data suggests that Kmt2a plays an important role in the structuring and wiring of the cortex, and when removed, can lead to brain disorders.

Presentation link

Interdisciplinary, Natural/Life Sciences

lsa logoum logo