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 guidan...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713000934 |
| _version_ | 1828475958456221696 |
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| author | Gunnar Newquist J. Michelle Drennan Matthew Lamanuzzi Kirsti Walker James C. Clemens Thomas Kidd |
| author_facet | Gunnar Newquist J. Michelle Drennan Matthew Lamanuzzi Kirsti Walker James C. Clemens Thomas Kidd |
| author_sort | Gunnar Newquist |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:21:39Z |
| format | Article |
| id | doaj.art-e0ea2b4ecc804dfd8aa028f0f1e5d2b7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T06:21:39Z |
| publishDate | 2013-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e0ea2b4ecc804dfd8aa028f0f1e5d2b72022-12-22T01:17:49ZengElsevierCell Reports2211-12472013-03-013359560610.1016/j.celrep.2013.02.017Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin MutantsGunnar Newquist0J. Michelle Drennan1Matthew Lamanuzzi2Kirsti Walker3James C. Clemens4Thomas Kidd5Department of Biology, University of Nevada, Reno, NV 89557, USADepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USADepartment of Biology, University of Nevada, Reno, NV 89557, USADepartment of Biology, University of Nevada, Reno, NV 89557, USADepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USADepartment of Biology, University of Nevada, Reno, NV 89557, USANetrins 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.http://www.sciencedirect.com/science/article/pii/S2211124713000934 |
| spellingShingle | Gunnar Newquist J. Michelle Drennan Matthew Lamanuzzi Kirsti Walker James C. Clemens Thomas Kidd Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants Cell Reports |
| title | Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants |
| title_full | Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants |
| title_fullStr | Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants |
| title_full_unstemmed | Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants |
| title_short | Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants |
| title_sort | blocking apoptotic signaling rescues axon guidance in netrin mutants |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713000934 |
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