Preprint Review Version 1 This version is not peer-reviewed

The Role of Apoptotic Signaling in Axon Guidance

Version 1 : Received: 15 September 2018 / Approved: 16 September 2018 / Online: 16 September 2018 (09:43:52 CEST)

How to cite: Kellermeyer, R.; Heydman, L.M.; Mastick, G.S.; Kidd, T. The Role of Apoptotic Signaling in Axon Guidance. Preprints 2018, 2018090281 (doi: 10.20944/preprints201809.0281.v1). Kellermeyer, R.; Heydman, L.M.; Mastick, G.S.; Kidd, T. The Role of Apoptotic Signaling in Axon Guidance. Preprints 2018, 2018090281 (doi: 10.20944/preprints201809.0281.v1).

Abstract

Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.

Subject Areas

axon guidance; growth cone; cytoskeleton; caspases; apoptosis; signal integration; basal level of caspase activity; death associated inhibitor of apoptosis; axon branching; Netrin; DCC; frazzled; slit; robo; Drosophila

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