Genetic dissection of neuronal pattern formation

Neurological diseases and disorders have been estimated to affect 3.6 million Canadians living in the community and over 170,000 Canadians living in long-term care facilities, including in British Columbia. However, we have limited information about the molecular mechanisms that cause many of those neurological conditions, largely because of the complexity of our nervous system. Therefore, understanding the mechanical processes that impart precise neural circuit formation using a simple model organism is critical to try to find ways to prevent neurological diseases and cure patients.

Toward this goal, Dr. Mizumoto will use nematode Caenorhabditis elegans as a model system to investigate the mechanisms that underlie neuronal circuit development. C. elegans has a short life cycle (3 days/generation) with a simple nervous system consisting of only 302 neurons, making it a great genetic model system to study the fine neural circuit formation. Most importantly, countless studies have shown that mechanisms and molecular machineries underlying the development of the nervous system are remarkably conserved between C. elegans and humans. It is likely that the knowledge obtained from our research will be directly applicable to the human nervous system and to diseases associated with nervous system defects.

Using C. elegans, Dr. Mizumoto will explore how neurons communicate with their neighboring neurons/cells to form a stereotyped neuronal pattern at the level of single synapse, which is a specialized interface between neurons or between neurons and other type of cells (such as muscle cells), to transmit electrical signals. Using a combination of C. elegans genetics, molecular biology and microscopy, this research will move towards an understanding of the fundamental principles of neural network formation.These studies will advance health-related knowledge by providing direct targets for other researchers to test in fruit fly (Drosophila) and mammalian models of neurodevelopmental disorders affected by Sema/Plexin signaling and others, and ultimately the development of therapeutic strategies for the treatment of these disorders.

End of Award Update: April 2023

Most exciting outputs

Many of the genes that we discovered from our research in specifying synapse formation are heavily associated with various neurological conditions, which suggest that our work may have potential to better understand the disease conditions affected by mutations in these genes.

Impact so far

As our work is fundamental and basic, we do not expect the impact of our work to be immediate.

Potential influence

We hope that our discoveries would lead to the development of therapeutics to treat neurological conditions in 20 years.

Next steps

We will continue to uncover the fundamental mechanisms of synapse pattern formation and specificity using C. elegans as a model organism.