Project summary
Despite decades of research uncovering the basis of neurogenesis during development, we do not know as
much about neurogenesis in a regenerative context. Regeneration, or the ability to regrow lost tissue, is a rare
feat in the animal kingdom. Although humans can replenish few cell types in the adult brain, they do not have
the ability to regrow large sections of tissue after injury. Improved regenerative therapies would benefit patients
who have experienced stroke, neurodegenerative disease, or traumatic injury. Because the human brain
regenerates itself poorly, our lab seeks to explore fundamental principles of successful brain regeneration
using organisms that can regenerate – planarians. Planarian flatworms regenerate all their body structures,
including a brain, over the course of a week. However, we currently understand little about the genetic
mechanisms governing neural regeneration in planarians. To uncover mechanisms of brain regeneration, this
proposal focuses on elucidating the timeline of dopaminergic neuron maturation and characterizing genes
important for dopaminergic neuron regeneration. A preliminary screen revealed two genes important for
regeneration of dopaminergic neurons in the planarian brain, lim only domain 3 (lmo3) and amyloid precursor
protein. To further study roles of these genes, I will perform the research outlined in this proposal. Aim 1: I will
establish a timeline of dopaminergic neuron maturation and regeneration. Aim 2: I will uncover the cellular
mechanism through which LMO3 promotes neuron regeneration. Aim 3: I will characterize the molecular
mechanism by which LMO3 impacts dopaminergic regeneration in the planarian brain. My studies will improve
our fundamental knowledge of planarian neural regeneration, outlining a path for elucidating the full genetic
mechanism behind creation of dopaminergic neurons from pluripotent stem cells in this fascinating organism.
My data will also establish a protocol for characterizing cellular lifespan and will create new protocols for
discovering new protein-protein interactions in planarians. The fundamental scientific knowledge gleaned from
the completed aims will reveal how successful regeneration of specific cell types is accomplished over time.
Future applications of this work could inform preclinical treatments for neurodegenerative disorders,
contributing to the promise and possibility of successful brain regeneration.