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UBC Theses and Dissertations

Deciphering the genetics mechanisms that inhibit synapse formation Fortes, Ethan


In animals, precise behavioural outputs require the development and maintenance of precise synaptic contacts between neurons and their cellular targets. Understanding how cells in the nervous system exhibit fine communication at the synapse level is crucial to elucidating principles underlying fine control in biological systems. The development and maintenance of precise synapses requires inhibitory mechanisms to prevent excessive neuronal inputs. Impaired inhibition of synapse formation is implicated in serious neurological conditions including autism spectrum disorder and intellectual disability. One mechanism for the inhibition of synapse formation involves Traf2- and NCK- Interacting Kinase (TNIK). Mammalian TNIK is required for proper axon guidance and cell migration, and more recently has been found by our group to negatively regulate the formation of synapses in C. elegans orthologue mig-15. However, the mechanism for mig-15-mediated loss of synapses is unknown. Here we show that mig-15/TNIK functions to inhibit synapse formation via wdr-24, a component of the GATOR2 complex upstream of TORC1, a master regulatory hub controlling growth and development. These results implicate TORC1 as a possible negative regulator of synapse formation and may lead to a deeper understanding of how a highly conserved growth and development signalling network controls the formation of neural circuits.

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