A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion
Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerizat...
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/109442 https://orcid.org/0000-0001-5063-8502 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826205112441241600 |
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| author | McConnell, Russell E. Van Veen, John Vidaki, Marina Kwiatkowski, Adam V Meyer, Aaron Samuel Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering McConnell, Russell E. Van Veen, John Vidaki, Marina Kwiatkowski, Adam V Meyer, Aaron Samuel Gertler, Frank |
| author_sort | McConnell, Russell E. |
| collection | MIT |
| description | Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor. |
| first_indexed | 2024-09-23T13:07:14Z |
| format | Article |
| id | mit-1721.1/109442 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:07:14Z |
| publishDate | 2017 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1094422022-09-28T12:07:50Z A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion McConnell, Russell E. Van Veen, John Vidaki, Marina Kwiatkowski, Adam V Meyer, Aaron Samuel Gertler, Frank Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT McConnell, Russell E. Van Veen, John Vidaki, Marina Kwiatkowski, Adam V Meyer, Aaron Samuel Gertler, Frank Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor. National Institutes of Health (U.S.) (Grant F32-CA165700) National Institutes of Health (U.S.) (Grant R01-GM068678) National Institutes of Health (U.S.) (Grant P30-CA014051) 2017-05-31T13:14:51Z 2017-05-31T13:14:51Z 2016-04 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/109442 McConnell, Russell E. et al. “A Requirement for Filopodia Extension toward Slit during Robo-Mediated Axon Repulsion.” The Journal of Cell Biology 213.2 (2016): 261–274. https://orcid.org/0000-0001-5063-8502 https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1083/jcb.201509062 The Journal of Cell Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | McConnell, Russell E. Van Veen, John Vidaki, Marina Kwiatkowski, Adam V Meyer, Aaron Samuel Gertler, Frank A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion |
| title | A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion |
| title_full | A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion |
| title_fullStr | A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion |
| title_full_unstemmed | A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion |
| title_short | A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion |
| title_sort | requirement for filopodia extension toward slit during robo mediated axon repulsion |
| url | http://hdl.handle.net/1721.1/109442 https://orcid.org/0000-0001-5063-8502 https://orcid.org/0000-0003-3214-4554 |
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