Abstract

During the development of the nervous system, neurons are guided to their final targets by several well-known guidance cues. In Caenorhabditis elegans the expression of the UNC-6/Netrin guidance cue along the ventral cord attracts axons that express UNC-40, while repulsing axons that express both the UNC-5 and UNC-40 receptors. Lack of both UNC-40 and the novel protein ENU-3 enhanced the ventral guidance defects of the AVM and PVM (Yee et al., 2014). This suggests that ENU-3 functions in an UNC-6 dependent pathway parallel to UNC-40 in controlling migrations towards the ventral nerve cord. Mutations in all proteins of the ENU-3 family also enhance the motor neuron axon outgrowth defects of strains lacking UNC-6 or the UNC-5 receptor, thus they function in a parallel unknown pathway (Yee et al., 2011). Expression analyses in HeLa cells have determined that ENU-3 and one of its paralogs, C38D4.1 localize to the nuclear membrane/ER while another of its paralogs, K01G5.3 is an intracellular membrane-associated protein.

Highlights

  • 1.1 General introduction and outline of thesisDuring the development of the nervous system, individual neuronal cell bodies project their axons towards their final targets, mediated by an interaction between instructive guidance cues and their respective receptors

  • Her data support the idea that the Enhancer of Uncoordinated phentotype-3 (ENU-3) proteins function redundantly to each other in supporting motor neuron axon outgrowth in the absence of UNC-5. She found that there were more defects when additional members of the family were depleted either by RNAi or genetically. Together these results suggest that all members of the ENU-3 protein family appear to have a role in affecting axon outgrowth of a subset of motor neurons in C. elegans that is independent of UNC-40, UNC-5 or UNC-6, suggesting they have roles in a novel unidentified pathway other than UNC-6/Netrin

  • The UNC-6/Netrin pathway is the mechanism by which several identified proteins function in order to control dorsal-ventral guidance of developing neurons, including the motor neurons and mechanosensory neurons examined in this thesis

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Summary

Introduction

During the development of the nervous system, individual neuronal cell bodies project their axons towards their final targets, mediated by an interaction between instructive guidance cues and their respective receptors. Growth cones at the tips of the axons of developing neurons express several receptors which can be either chemoattracted or chemo-repulsed by gradients of guidance cues in the extracellular environment. The highly stereotypical and intricate patterns involving growth, migration and development are followed by approximately one billion human neuronal cells and allow for connections even with distantly located cells. The interface between these cues and their receptors as well as how these interactions allow cells to make decisions regarding their correct migration pathways during development, are challenging aspects of the nervous system that are still under investigation. C. elegans, in which individual neurons can be observed in vivo in a simple nervous system and with a well understood genome, is the ideal model organism for nervous system analysis

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