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Cell Rep. 2013 Mar 28;3(3):595-606. doi: 10.1016/j.celrep.2013.02.017. Epub 2013 Mar 14.

Blocking apoptotic signaling rescues axon guidance in Netrin mutants.

Author information

1
Department of Biology, University of Nevada, Reno, NV 89557, USA.

Abstract

Netrins are guidance cues that form gradients to guide growing axons. We uncover a mechanism for axon guidance by demonstrating that axons can accurately navigate in the absence of a Netrin gradient if apoptotic signaling is blocked. Deletion of the two Drosophila NetA and NetB genes leads to guidance defects and increased apoptosis, and expression of either gene at the midline is sufficient to rescue the connectivity defects and cell death. Surprisingly, pan-neuronal expression of NetB rescues equally well, even though no Netrin gradient has been established. Furthermore, NetB expression blocks apoptosis, suggesting that NetB acts as a neurotrophic factor. In contrast, neuronal expression of NetA increases axon defects. Simply blocking apoptosis in NetAB mutants is sufficient to rescue connectivity, and inhibition of caspase activity in subsets of neurons rescues guidance independently of survival. In contrast to the traditional role of Netrin as simply a guidance cue, our results demonstrate that guidance and survival activities may be functionally related.

PMID:
23499445
PMCID:
PMC3777441
DOI:
10.1016/j.celrep.2013.02.017
[Indexed for MEDLINE]
Free PMC Article

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