Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism
The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (Sufu) plays a critical role in the establishment of the V-SVZ at early neona...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-06-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/8/6/bio039248 |
| _version_ | 1819075497421701120 |
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| author | Hector G. Gomez Hirofumi Noguchi Jesse Garcia Castillo David Aguilar Samuel J. Pleasure Odessa R. Yabut |
| author_facet | Hector G. Gomez Hirofumi Noguchi Jesse Garcia Castillo David Aguilar Samuel J. Pleasure Odessa R. Yabut |
| author_sort | Hector G. Gomez |
| collection | DOAJ |
| description | The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (Sufu) plays a critical role in the establishment of the V-SVZ at early neonatal stages by controlling the proliferation of distinct subpopulations of stem/precursor cells. Conditional deletion of Sufu in radial glial progenitor cells (RGCs) at E13.5 resulted in a dramatic increase in the proliferation of Sox2+ Type B1 cells. In contrast, we found a significant decrease in Gsx2+ and a more dramatic decrease in Tbr2+ transit amplifying cells (TACs) indicating that innate differences between dorsal and ventral forebrain derived Type B1 cells influence Sufu function. However, many precursors accumulated in the dorsal V-SVZ or failed to survive, demonstrating that despite the over-proliferation of Type B1 cells, they are unable to transition into functional differentiated progenies. These defects were accompanied by reduced Gli3 expression and surprisingly, a significant downregulation of Sonic hedgehog (Shh) signaling. Therefore, these findings indicate a potential role of the Sufu-Gli3 regulatory axis in the neonatal dorsal V-SVZ independent of Shh signaling in the establishment and survival of functional stem/precursor cells in the postnatal dorsal V-SVZ. |
| first_indexed | 2024-12-21T18:26:21Z |
| format | Article |
| id | doaj.art-a929ec87f1234eaa8032d053bd00a25c |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-21T18:26:21Z |
| publishDate | 2019-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-a929ec87f1234eaa8032d053bd00a25c2022-12-21T18:54:23ZengThe Company of BiologistsBiology Open2046-63902019-06-018610.1242/bio.039248039248Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanismHector G. Gomez0Hirofumi Noguchi1Jesse Garcia Castillo2David Aguilar3Samuel J. Pleasure4Odessa R. Yabut5 Department of Neurology Department of Neurology Department of Neurology Department of Neurology Department of Neurology Department of Neurology The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (Sufu) plays a critical role in the establishment of the V-SVZ at early neonatal stages by controlling the proliferation of distinct subpopulations of stem/precursor cells. Conditional deletion of Sufu in radial glial progenitor cells (RGCs) at E13.5 resulted in a dramatic increase in the proliferation of Sox2+ Type B1 cells. In contrast, we found a significant decrease in Gsx2+ and a more dramatic decrease in Tbr2+ transit amplifying cells (TACs) indicating that innate differences between dorsal and ventral forebrain derived Type B1 cells influence Sufu function. However, many precursors accumulated in the dorsal V-SVZ or failed to survive, demonstrating that despite the over-proliferation of Type B1 cells, they are unable to transition into functional differentiated progenies. These defects were accompanied by reduced Gli3 expression and surprisingly, a significant downregulation of Sonic hedgehog (Shh) signaling. Therefore, these findings indicate a potential role of the Sufu-Gli3 regulatory axis in the neonatal dorsal V-SVZ independent of Shh signaling in the establishment and survival of functional stem/precursor cells in the postnatal dorsal V-SVZ.http://bio.biologists.org/content/8/6/bio039248NeurogenesisProliferationVentricular-subventricular zoneV-SVZSufuGli3 |
| spellingShingle | Hector G. Gomez Hirofumi Noguchi Jesse Garcia Castillo David Aguilar Samuel J. Pleasure Odessa R. Yabut Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism Biology Open Neurogenesis Proliferation Ventricular-subventricular zone V-SVZ Sufu Gli3 |
| title | Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism |
| title_full | Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism |
| title_fullStr | Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism |
| title_full_unstemmed | Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism |
| title_short | Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism |
| title_sort | suppressor of fused regulates the proliferation of postnatal neural stem and precursor cells via a gli3 dependent mechanism |
| topic | Neurogenesis Proliferation Ventricular-subventricular zone V-SVZ Sufu Gli3 |
| url | http://bio.biologists.org/content/8/6/bio039248 |
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