Understanding the role of Wnt signaling in neural stem cell trajectories during injury induced regeneration

Authors

• BM Brooks
• W Heavner
• J Ngai

Abstract

We have all recognized the importance of our sense of smell with the recent pandemic. What happens when the neurons in your nose die due to illness,injury, or environmental factors? In an evolutionarily conserved process called neurogenesis, adult mammals develop functional neurons from neural stem cells that can generate new neurons throughout life.The olfactory epithelium(OE) is a stem cell niche where this occurs due to its unique exposure to the outside environment; requiring that upon injury, repair mechanisms activate to maintain the epithelium.
The mouseOE, due to its accessibility and robust response to acute injury, is a tractable model for studying the molecular mechanisms that drive neural regeneration.We have shown previously that canonical Wnt signaling plays a role in olfactory stem cell proliferation, driving OEstem cells toward a neural fate. Also,it has been shown that Wnt signaling is necessary and sufficient to drive olfactory stem cells from resting to activated in uninjuredOE.
In this study,we will use clonal lineage tracing, with single-cell sequencing to identify the major regulators of Wnt signaling in olfactory stem cell fate after injury.This will illuminate how Wntsignaling regulates regeneration of the OE under injury and steady-state conditions. Specifically, we plan to identify the components of the gene regulatory networks that are disrupted after GOF/LOF of Wntsignaling during mouseOE regeneration.We will also test candidate molecular modulators of Wntsignaling in an in vitro OE culture system. These data, along with successive work, will contribute to the understanding of how Wntsignaling regulates the regenerative capacity of the OE.

Scientific Focus Area: Neuroscience

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