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The kinase-independent roles of the C. elegans Eph receptor in axon guidance involve PI 3-kinase and the Abl tyrosine kinase

  • Author(s): Grossman, Emily Nicole
  • et al.

It is only within the last twenty years that scientists have begun to understand the processes of axon guidance. Although a considerable body of work has been published regarding the mechanisms of axon guidance, much is still not known. In this work we seek to elucidate the in vivo mechanism of ephrin signaling, using the amphid sensory neurons of Caenorhabditis elegans as a model. In contrast to mammalian models, C. elegans only encodes a single Eph receptor, VAB-1. We find that guidance of the amphid neurons requires both kinase-dependent and kinase- independent Eph signaling mediated by EFN-1, a GPI-linked ligand. Expression of VAB-1 was observed in select amphid neurons, and EFN-1 expression was visible in surrounding cells. This expression pattern is consistent with a model of kinase-independent forward Eph signaling by VAB-1. We find that the phosphatidylinositol 3-kinase pathway and the ABL-1 non-receptor tyrosine kinase have roles in this Eph kinase-independent pathway. Surprisingly, we identified an asymmetry in guidance defects where left- hand neurons are affected significantly more often than right-hand neurons by loss of Eph signaling. Additionally, we find that overexpression of ABL-1 in a single neuron pair can rescue the entire sensory bundle, suggesting a non-cell autonomous relationship between the amphids during outgrowth. Lastly, we report our observation that a hyperactive calcium channel mutant, in combination with ephrin signaling mutants, cause disruption of dendrite attachment. These results shed light on the in vivo mechanisms of Eph signaling, and uncover previously unknown roles for ABL-1 in C. elegans

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