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Wnt and gap junction proteins cooperatively regulate axonal and presynaptic tiling in Caenorhabditis elegans Hendi, Ardalan

Abstract

Precise synaptic connection of neurons with their targets is essential for the proper functioning of the nervous system. A plethora of signaling pathways act in concert to mediate the precise spatial arrangement of synaptic connections. One method of ensuring proper wiring in the nervous system is through neuronal tiling. Neuronal tiling is a phenomenon in which neurons project axons and dendrites without overlapping with those of neighbouring neurons within the same class. While neuronal tiling is observed in several types of neurons across species, the molecular mechanisms remain less studied. My thesis aims to uncover the molecular mechanisms underlying neuronal tiling using C. elegans as a model organism, in which neuronal tiling is present in the GABAergic motor neurons. I found that axonal tiling between two neighbouring GABAergic motor neurons is regulated by a Wnt morphogen. However, disrupting axonal tiling did not affect presynaptic tiling between the two neurons. I showed that presynaptic tiling is controlled by a gap junction protein, UNC-9, which is localized at the presynaptic tiling border between neighbouring DD neurons. Strikingly, the gap junction channel activity of UNC- 9 is dispensable for its function in controlling tiled presynaptic patterning. While gap junctions are crucial for the proper functioning of the nervous system as channels, my findings uncovered the novel channel-independent role of UNC-9 in presynaptic patterning.

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