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This week we profile a recent publication in eLife from the laboratory of Dr. Kota Mizumoto (pictured, right) at UBC.

Can you provide a brief overview of your lab’s current research focus?

Our lab focuses on elucidating the genetic and molecular basis that underlies the development of our nervous system. During nervous system development, individual nerve cells (neurons) send long processes (axons and dendrites) to their target cells to form a specialized cell-cell connection called synapses through which neurons send/receive information. We are interested in understanding how neurons use information from their surrounding environment, including the neighboring cells, during nervous system development. Toward this, we use a free-living nematode, Caenorhabditis elegans, as a genetic model organism. C. elegans has a simple nervous system, yet its development and function are highly conserved to those in humans, allowing us to explore the fundamental principles of nervous system development efficiently.

What is the significance of the findingsĀ inĀ this publication?

When neurons extend their processes, they often make excessive number of neurites at early stages of development. Later, neurons eliminate unnecessary neurites by a mechanism called neurite pruning. In the present study, we reported that the stereotyped neurite pruning is regulated by a secreted protein, Wnt, and its receptor protein, Frizzled. Wnt is one of the best-studied morphogenic signalling molecules that plays pivotal roles in animal development including stem cell maintenance and cell polarization. On the other hand, only a few studies have shown its roles in neurite pruning. Using genetic approaches including CRISPR/Cas9 genome editing technology, we found that neurite pruning is induced only when the neurites are in close proximity to the cells expressing Wnt, suggesting that unlike many other Wnt-dependent morphogenic events that depend on gradient distribution of the Wnt protein in the tissue, neurite pruning does not require a Wnt gradient. Rather, it is induced only at the surface of the Wnt-producing cells, possibly because local high-concentration of Wnt is required to induce neurite pruning. We also found that the same neuron can respond to the Wnt gradient in order to determine the position of its synapses, suggesting that a cell can utilize gradient-dependent and independent Wnt signalling in context-dependent manners.

What are the next steps for this research?

We showed a novel role of Wnt signalling that instructs neurite pruning. The obvious next step is to understand the downstream mechanisms that execute the pruning process. We are also curious to know if the function of Wnt signalling in neurite pruning is conserved in other organisms, including mammals. It is also interesting to explore the gradient-independent functions of Wnt signalling in other developmental processes such as asymmetric cell division, cell polarization and axon guidance. There are five Wnt genes that control distinct biological processes in the C. elegans genome. We are curious to know which Wnts function as gradient cues and gradient-independent cues.

This work was funded by:

NSERC, HFSP

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