Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway
In neurons, the acquisition of a polarized morphology is achieved upon the outgrowth of a single axon from one of several neurites. Small extracellular vesicles (sEVs), such as exosomes, from diverse sources are known to promote neurite outgrowth and thus may have therapeutic potential. However, the...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/1/56 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841549313874853888 |
|---|---|
| author | Samar Ahmad Tania Christova Melanie Pye Masahiro Narimatsu Siyuan Song Jeffrey L. Wrana Liliana Attisano |
| author_facet | Samar Ahmad Tania Christova Melanie Pye Masahiro Narimatsu Siyuan Song Jeffrey L. Wrana Liliana Attisano |
| author_sort | Samar Ahmad |
| collection | DOAJ |
| description | In neurons, the acquisition of a polarized morphology is achieved upon the outgrowth of a single axon from one of several neurites. Small extracellular vesicles (sEVs), such as exosomes, from diverse sources are known to promote neurite outgrowth and thus may have therapeutic potential. However, the effect of fibroblast-derived exosomes on axon elongation in neurons of the central nervous system under growth-permissive conditions remains unclear. Here, we show that fibroblast-derived sEVs promote axon outgrowth and a polarized neuronal morphology in mouse primary embryonic cortical neurons. Mechanistically, we demonstrate that the sEV-induced increase in axon outgrowth requires endogenous Wnts and core PCP components including Prickle, Vangl, Frizzled, and Dishevelled. We demonstrate that sEVs are internalized by neurons, colocalize with Wnt7b, and induce relocalization of Vangl2 to the distal axon during axon outgrowth. In contrast, sEVs derived from neurons or astrocytes do not promote axon outgrowth, while sEVs from activated astrocytes inhibit elongation. Thus, our data reveal that fibroblast-derived sEVs promote axon elongation through the Wnt-PCP pathway in a manner that is dependent on endogenous Wnts. |
| format | Article |
| id | doaj-art-f08a3b5977a44a478863bd8ff874006f |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-f08a3b5977a44a478863bd8ff874006f2025-01-10T13:16:23ZengMDPI AGCells2073-44092025-01-011415610.3390/cells14010056Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity PathwaySamar Ahmad0Tania Christova1Melanie Pye2Masahiro Narimatsu3Siyuan Song4Jeffrey L. Wrana5Liliana Attisano6Department of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaDepartment of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaCenter for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, CanadaCenter for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, CanadaDepartment of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaCenter for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, CanadaDepartment of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, CanadaIn neurons, the acquisition of a polarized morphology is achieved upon the outgrowth of a single axon from one of several neurites. Small extracellular vesicles (sEVs), such as exosomes, from diverse sources are known to promote neurite outgrowth and thus may have therapeutic potential. However, the effect of fibroblast-derived exosomes on axon elongation in neurons of the central nervous system under growth-permissive conditions remains unclear. Here, we show that fibroblast-derived sEVs promote axon outgrowth and a polarized neuronal morphology in mouse primary embryonic cortical neurons. Mechanistically, we demonstrate that the sEV-induced increase in axon outgrowth requires endogenous Wnts and core PCP components including Prickle, Vangl, Frizzled, and Dishevelled. We demonstrate that sEVs are internalized by neurons, colocalize with Wnt7b, and induce relocalization of Vangl2 to the distal axon during axon outgrowth. In contrast, sEVs derived from neurons or astrocytes do not promote axon outgrowth, while sEVs from activated astrocytes inhibit elongation. Thus, our data reveal that fibroblast-derived sEVs promote axon elongation through the Wnt-PCP pathway in a manner that is dependent on endogenous Wnts.https://www.mdpi.com/2073-4409/14/1/56extracellular vesiclesaxon outgrowthplanar cell polarityneurite outgrowthcortical neurons |
| spellingShingle | Samar Ahmad Tania Christova Melanie Pye Masahiro Narimatsu Siyuan Song Jeffrey L. Wrana Liliana Attisano Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway Cells extracellular vesicles axon outgrowth planar cell polarity neurite outgrowth cortical neurons |
| title | Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway |
| title_full | Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway |
| title_fullStr | Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway |
| title_full_unstemmed | Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway |
| title_short | Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway |
| title_sort | small extracellular vesicles promote axon outgrowth by engaging the wnt planar cell polarity pathway |
| topic | extracellular vesicles axon outgrowth planar cell polarity neurite outgrowth cortical neurons |
| url | https://www.mdpi.com/2073-4409/14/1/56 |
| work_keys_str_mv | AT samarahmad smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway AT taniachristova smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway AT melaniepye smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway AT masahironarimatsu smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway AT siyuansong smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway AT jeffreylwrana smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway AT lilianaattisano smallextracellularvesiclespromoteaxonoutgrowthbyengagingthewntplanarcellpolaritypathway |