Genetic sparse cell labeling in the cerebral cortex – UROP Spring Symposium 2022

Genetic sparse cell labeling in the cerebral cortex

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Maeve Lucas

Pronouns: she/her/hers

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: Maeve C Lucas, Daniel Z Doyle, Kenneth Y Kwan
Presenter: 52

Abstract

Proper brain function relies on a diverse set of neurons with unique connectivities. The morphology of individual neurons is thus critical to their function within the brain. However, neurons are densely packed throughout the brain, therefore impairing our ability to identify individual morphologies. In an attempt to resolve neuronal structure, sparse labeling techniques such as Golgi’s method have been used over the past 150 years. While this has become more commonly leveraged, Golgi’s method takes multiple weeks to complete, is not cell type-specific, and the reagents preclude the use of co-labeling for any protein markers to examine the molecular identity of the neurons being labeled. To circumvent these limitations, a group recently generated improved mouse lines for Cre-dependent fluorescent sparse labeling using mononucleotide repeat frameshift (MORF) (Veldman et al., 2020). This new tool enables us to collaboratively visualize all Cre-positive neurons at a population level with commonly used Cre-dependent reporter lines, such as Ai14, while simultaneously sparsely labeling Cre-positive cells with the MORF1 line. We find that the Tg(Rbp4-Cre) and Ntsr1Cre mouse lines, which are expressed in layers 5 and 6 of the cerebral cortex, respectively, as well as the dentate gyrus of the hippocampus, are both effective in producing widespread and sparse labeling with Ai14 and MORF1. Together our data illustrate that these tools provide exceptional resolution and will enable in-depth investigation of neuronal morphologies in mouse models of neurodevelopmental disorders such as autism and schizophrenia.

Presentation link

Interdisciplinary, Natural/Life Sciences

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