Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair
Summary: Schwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined, and consequently, it is unclear whether this f...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723012949 |
| _version_ | 1797448121879363584 |
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| author | Lydia Daboussi Giancarlo Costaguta Miriam Gullo Nicole Jasinski Veronica Pessino Brendan O’Leary Karen Lettieri Shawn Driscoll Samuel L. Pfaff |
| author_facet | Lydia Daboussi Giancarlo Costaguta Miriam Gullo Nicole Jasinski Veronica Pessino Brendan O’Leary Karen Lettieri Shawn Driscoll Samuel L. Pfaff |
| author_sort | Lydia Daboussi |
| collection | DOAJ |
| description | Summary: Schwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined, and consequently, it is unclear whether this form of cellular plasticity has a role in peripheral neuropathies. Here, we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling. Mitf regulates a core transcriptional program for generating functional repair Schwann cells following injury and during peripheral neuropathies caused by CMT4J and CMT4D. In the absence of Mitf, core genes for epithelial-to-mesenchymal transition, metabolism, and dedifferentiation are misexpressed, and nerve repair is disrupted. Our findings demonstrate that Schwann cells monitor axonal health using a phosphoinositide signaling system that controls Mitf nuclear localization, which is critical for activating cellular plasticity and counteracting neural disease. |
| first_indexed | 2024-03-09T14:05:53Z |
| format | Article |
| id | doaj.art-6cfe1dba7eb04f18adfa9d368ab31218 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:05:53Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6cfe1dba7eb04f18adfa9d368ab312182023-11-30T05:06:39ZengElsevierCell Reports2211-12472023-11-014211113282Mitf is a Schwann cell sensor of axonal integrity that drives nerve repairLydia Daboussi0Giancarlo Costaguta1Miriam Gullo2Nicole Jasinski3Veronica Pessino4Brendan O’Leary5Karen Lettieri6Shawn Driscoll7Samuel L. Pfaff8Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USAGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA; Corresponding authorSummary: Schwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined, and consequently, it is unclear whether this form of cellular plasticity has a role in peripheral neuropathies. Here, we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling. Mitf regulates a core transcriptional program for generating functional repair Schwann cells following injury and during peripheral neuropathies caused by CMT4J and CMT4D. In the absence of Mitf, core genes for epithelial-to-mesenchymal transition, metabolism, and dedifferentiation are misexpressed, and nerve repair is disrupted. Our findings demonstrate that Schwann cells monitor axonal health using a phosphoinositide signaling system that controls Mitf nuclear localization, which is critical for activating cellular plasticity and counteracting neural disease.http://www.sciencedirect.com/science/article/pii/S2211124723012949CP: Neuroscience |
| spellingShingle | Lydia Daboussi Giancarlo Costaguta Miriam Gullo Nicole Jasinski Veronica Pessino Brendan O’Leary Karen Lettieri Shawn Driscoll Samuel L. Pfaff Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair Cell Reports CP: Neuroscience |
| title | Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair |
| title_full | Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair |
| title_fullStr | Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair |
| title_full_unstemmed | Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair |
| title_short | Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair |
| title_sort | mitf is a schwann cell sensor of axonal integrity that drives nerve repair |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723012949 |
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