Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila
Neuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits. Channelrhodopsin-based optogenetics shows the feasibility of stimulating neural repair but does not pin down specific signaling cascades. Here, we utilized optogenetic systems, optoRaf and opto...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/57395 |
| _version_ | 1811253125079629824 |
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| author | Qin Wang Huaxun Fan Feng Li Savanna S Skeeters Vishnu V Krishnamurthy Yuanquan Song Kai Zhang |
| author_facet | Qin Wang Huaxun Fan Feng Li Savanna S Skeeters Vishnu V Krishnamurthy Yuanquan Song Kai Zhang |
| author_sort | Qin Wang |
| collection | DOAJ |
| description | Neuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits. Channelrhodopsin-based optogenetics shows the feasibility of stimulating neural repair but does not pin down specific signaling cascades. Here, we utilized optogenetic systems, optoRaf and optoAKT, to delineate the contribution of the ERK and AKT signaling pathways to neuroregeneration in live Drosophila larvae. We showed that optoRaf or optoAKT activation not only enhanced axon regeneration in both regeneration-competent and -incompetent sensory neurons in the peripheral nervous system but also allowed temporal tuning and proper guidance of axon regrowth. Furthermore, optoRaf and optoAKT differ in their signaling kinetics during regeneration, showing a gated versus graded response, respectively. Importantly in the central nervous system, their activation promotes axon regrowth and functional recovery of the thermonociceptive behavior. We conclude that non-neuronal optogenetics targets damaged neurons and signaling subcircuits, providing a novel strategy in the intervention of neural damage with improved precision. |
| first_indexed | 2024-04-12T16:45:59Z |
| format | Article |
| id | doaj.art-3baaadab5ede46b4aebf1584ee3ad5af |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:45:59Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3baaadab5ede46b4aebf1584ee3ad5af2022-12-22T03:24:35ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.57395Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in DrosophilaQin Wang0Huaxun Fan1Feng Li2Savanna S Skeeters3Vishnu V Krishnamurthy4https://orcid.org/0000-0001-9905-5965Yuanquan Song5https://orcid.org/0000-0001-7699-2059Kai Zhang6https://orcid.org/0000-0002-6687-4558Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biochemistry, Urbana, United StatesRaymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biochemistry, Urbana, United StatesDepartment of Biochemistry, Urbana, United StatesRaymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biochemistry, Urbana, United States; Neuroscience Program, Urbana, United States; Center for Biophysics and Quantitative Biology, Urbana, United States; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, United StatesNeuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits. Channelrhodopsin-based optogenetics shows the feasibility of stimulating neural repair but does not pin down specific signaling cascades. Here, we utilized optogenetic systems, optoRaf and optoAKT, to delineate the contribution of the ERK and AKT signaling pathways to neuroregeneration in live Drosophila larvae. We showed that optoRaf or optoAKT activation not only enhanced axon regeneration in both regeneration-competent and -incompetent sensory neurons in the peripheral nervous system but also allowed temporal tuning and proper guidance of axon regrowth. Furthermore, optoRaf and optoAKT differ in their signaling kinetics during regeneration, showing a gated versus graded response, respectively. Importantly in the central nervous system, their activation promotes axon regrowth and functional recovery of the thermonociceptive behavior. We conclude that non-neuronal optogenetics targets damaged neurons and signaling subcircuits, providing a novel strategy in the intervention of neural damage with improved precision.https://elifesciences.org/articles/57395optogeneticsaxon regenerationDrosophiladendritic arborizationsensory neuronsthermonociception |
| spellingShingle | Qin Wang Huaxun Fan Feng Li Savanna S Skeeters Vishnu V Krishnamurthy Yuanquan Song Kai Zhang Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila eLife optogenetics axon regeneration Drosophila dendritic arborization sensory neurons thermonociception |
| title | Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila |
| title_full | Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila |
| title_fullStr | Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila |
| title_full_unstemmed | Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila |
| title_short | Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila |
| title_sort | optical control of erk and akt signaling promotes axon regeneration and functional recovery of pns and cns in drosophila |
| topic | optogenetics axon regeneration Drosophila dendritic arborization sensory neurons thermonociception |
| url | https://elifesciences.org/articles/57395 |
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