FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord.
Wnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β -catenin-dependent, signaling by binding to Frizzled receptors. However, in...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0219721 |
| _version_ | 1818833471734284288 |
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| author | Abdulmajeed Fahad Alrefaei Andrea E Münsterberg Grant N Wheeler |
| author_facet | Abdulmajeed Fahad Alrefaei Andrea E Münsterberg Grant N Wheeler |
| author_sort | Abdulmajeed Fahad Alrefaei |
| collection | DOAJ |
| description | Wnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β -catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6. |
| first_indexed | 2024-12-19T02:19:27Z |
| format | Article |
| id | doaj.art-305c9f777b654b6cac6ee97d14cdbc43 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T02:19:27Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-305c9f777b654b6cac6ee97d14cdbc432022-12-21T20:40:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01156e021972110.1371/journal.pone.0219721FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord.Abdulmajeed Fahad AlrefaeiAndrea E MünsterbergGrant N WheelerWnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β -catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6.https://doi.org/10.1371/journal.pone.0219721 |
| spellingShingle | Abdulmajeed Fahad Alrefaei Andrea E Münsterberg Grant N Wheeler FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. PLoS ONE |
| title | FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. |
| title_full | FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. |
| title_fullStr | FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. |
| title_full_unstemmed | FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. |
| title_short | FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. |
| title_sort | fzd10 regulates cell proliferation and mediates wnt1 induced neurogenesis in the developing spinal cord |
| url | https://doi.org/10.1371/journal.pone.0219721 |
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