Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination
Peripheral myelination is driven by the intricate interplay between Schwann cells and axons, coordinated through molecular signaling and the structural organization of their shared environment. While the biochemical regulation of this process has been extensively studied, the influence of spatial ar...
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MDPI AG
2025-06-01
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| author | Luca Bartesaghi Basilio Giangreco Vanessa Chiappini Maria Fernanda Veloz Castillo Martina Monaco Jean-Jaques Médard Giovanna Gambarotta Marco Agus Corrado Calì |
| author_facet | Luca Bartesaghi Basilio Giangreco Vanessa Chiappini Maria Fernanda Veloz Castillo Martina Monaco Jean-Jaques Médard Giovanna Gambarotta Marco Agus Corrado Calì |
| author_sort | Luca Bartesaghi |
| collection | DOAJ |
| description | Peripheral myelination is driven by the intricate interplay between Schwann cells and axons, coordinated through molecular signaling and the structural organization of their shared environment. While the biochemical regulation of this process has been extensively studied, the influence of spatial architecture and mechanical cues remains poorly understood. Here, we use in vitro co-culture models—featuring microfluidic devices and hydrogel-based scaffolds—to explore how extracellular organization, cellular density, and spatial constraints shape Schwann cell behavior. Our results show that (i) pro-myelinating effects triggered by ascorbic acid administration is distally propagated along axons in Schwann cell-DRG co-cultures, (ii) ascorbic acid modulates Neuregulin-1 expression, (iii) a critical threshold of cellular density is required to support proper Schwann cell differentiation and myelin formation, and (iv) spatial confinement promotes myelination in the absence of ascorbic acid. Together, these findings highlight how spatial and structural parameters regulate the cellular and molecular events underlying peripheral myelination, offering new physiologically relevant models of myelination and opening new avenues for peripheral nerve repair strategies. |
| format | Article |
| id | doaj-art-cbe29a66ca8d4673bfb59eaab0968fde |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-cbe29a66ca8d4673bfb59eaab0968fde2025-08-20T02:24:29ZengMDPI AGCells2073-44092025-06-01141292610.3390/cells14120926Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral MyelinationLuca Bartesaghi0Basilio Giangreco1Vanessa Chiappini2Maria Fernanda Veloz Castillo3Martina Monaco4Jean-Jaques Médard5Giovanna Gambarotta6Marco Agus7Corrado Calì8Department of Neuroscience “Rita Levi Montalcini”, University of Turin, 10124 Torino, ItalyCenter for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), 1015 Lausanne, SwitzerlandDepartment of Neuroscience “Rita Levi Montalcini”, University of Turin, 10124 Torino, ItalyDepartment of Neuroscience “Rita Levi Montalcini”, University of Turin, 10124 Torino, ItalyNeuroscience Institute Cavalieri Ottolenghi, Regione Gonzole 10, 10043 Orbassano, ItalyCancer Research Center of Lyon (CRCL), Inserm U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, 69008 Lyon, FranceNeuroscience Institute Cavalieri Ottolenghi, Regione Gonzole 10, 10043 Orbassano, ItalyCollege of Science and Engineering, Hamad Bin Khalifa University, LAS Building, Doha P.O Box 5825, QatarDepartment of Neuroscience “Rita Levi Montalcini”, University of Turin, 10124 Torino, ItalyPeripheral myelination is driven by the intricate interplay between Schwann cells and axons, coordinated through molecular signaling and the structural organization of their shared environment. While the biochemical regulation of this process has been extensively studied, the influence of spatial architecture and mechanical cues remains poorly understood. Here, we use in vitro co-culture models—featuring microfluidic devices and hydrogel-based scaffolds—to explore how extracellular organization, cellular density, and spatial constraints shape Schwann cell behavior. Our results show that (i) pro-myelinating effects triggered by ascorbic acid administration is distally propagated along axons in Schwann cell-DRG co-cultures, (ii) ascorbic acid modulates Neuregulin-1 expression, (iii) a critical threshold of cellular density is required to support proper Schwann cell differentiation and myelin formation, and (iv) spatial confinement promotes myelination in the absence of ascorbic acid. Together, these findings highlight how spatial and structural parameters regulate the cellular and molecular events underlying peripheral myelination, offering new physiologically relevant models of myelination and opening new avenues for peripheral nerve repair strategies.https://www.mdpi.com/2073-4409/14/12/926peripheral nervous system (PNS)Schwann cellsmyelinneuregulin-1 (NRG-1)in vitro modelsmicrofluidic chambers |
| spellingShingle | Luca Bartesaghi Basilio Giangreco Vanessa Chiappini Maria Fernanda Veloz Castillo Martina Monaco Jean-Jaques Médard Giovanna Gambarotta Marco Agus Corrado Calì Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination Cells peripheral nervous system (PNS) Schwann cells myelin neuregulin-1 (NRG-1) in vitro models microfluidic chambers |
| title | Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination |
| title_full | Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination |
| title_fullStr | Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination |
| title_full_unstemmed | Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination |
| title_short | Tight Spaces, Tighter Signals: Spatial Constraints as Drivers of Peripheral Myelination |
| title_sort | tight spaces tighter signals spatial constraints as drivers of peripheral myelination |
| topic | peripheral nervous system (PNS) Schwann cells myelin neuregulin-1 (NRG-1) in vitro models microfluidic chambers |
| url | https://www.mdpi.com/2073-4409/14/12/926 |
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