Analysis of the Kekkon Family in Neuronal Development

Plada, Edith Vanina Machado

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Analysis of the Kekkon Family in Neuronal Development

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Adhesion Molecules have been associated with a number of neurological and psychological disorders (humans), and implicated in various developmental processes (animals). Better understanding the development of the nervous system and the roles of adhesion molecules in it may be crucial to better understanding these disorders. LIGs, Leucine Rich Repeat and ImmunoGlobulin containing transmembrane proteins, represent a novel class of such adhesion molecules and have been implicated in various neuronal processes, including neurite outgrowth, axonal pathfinding, neuronal regeneration and survival. Two such LIGs are Kek1 and Kek2, members of a Drosophila LIG family, which have been reported to function in axonal pathfinding and synaptic plasticity, respectively. It is unclear what their roles in these processes are, as well as if other members of the Drosophila LIG family have similar roles. Current studies aim to survey the Kekkon family function in the nervous system, looking to identify new phenotypes and/or to elucidate the mechanisms underlying previously identified phenotypes. To achieve this goal, tissue specific inducible RNAi technique was employed. Validating of a number of transgenic RNAi stocks obtained was necessary and showed that all stocks obtained promoted specific and efficient knock down of target gene. Next an assessment of RNAi knockdown efficacy in developing nervous system was carried out and knockdown was shown to be weak if not in the presence of Dicer-2 co-misexpression. A number of screens for general behavioral phenotypes were performed including ubiquitous, neural, and imaginal discs knockdown. These uncovered possible effects of kek1 neural knockdown, as well as possible interaction of Kek1 with neurotactin, neuroglian and kek2. NMJ analysis of Kek5 and Kek6 was also carried out and preliminary results indicate possible interaction of kek5 in NMJ, although no statistical significance was detected.

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