Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants
Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants
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.
- Purdue University West Lafayette United States
- Purdue University Northwest United States
- Purdue University System United States
- Department of Biology United States
- UNIVERSITY OF NEVADA RENO
QH301-705.5, Tumor Suppressor Proteins, Apoptosis, Netrin-1, Axons, Mutation, Animals, Drosophila Proteins, Drosophila, Netrins, Nerve Growth Factors, Biology (General), Signal Transduction
QH301-705.5, Tumor Suppressor Proteins, Apoptosis, Netrin-1, Axons, Mutation, Animals, Drosophila Proteins, Drosophila, Netrins, Nerve Growth Factors, Biology (General), Signal Transduction
98 Research products, page 1 of 10
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).20 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
