Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration
Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of t...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2026-03-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00623 |
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| author | Kierra Ware Joshua Peter Lucas McClain Yu Luo |
| author_facet | Kierra Ware Joshua Peter Lucas McClain Yu Luo |
| author_sort | Kierra Ware |
| collection | DOAJ |
| description | Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of transforming growth factor-β signaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo, we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-β signaling in neural stem cells in (mGFAPcre-ALK5fl/fl-Ai9) or immature neuroblasts in (DCXcreERT2-ALK5fl/fl-Ai9). Our data showed that exogenous transforming growth factor-β treatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration. These effects were abolished in activin-like kinase 5 (ALK5) knockout primary neural stem cells. Consistent with this, inhibition of transforming growth factor-β signaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells. Interestingly, deletion of transforming growth factor-β receptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice, while abolishment of transforming growth factor-β signaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus. In summary, our data supports a dual role of transforming growth factor-β signaling in the proliferation and migration of neural stem cells in vitro. Moreover, our data provides novel insights on cell type–specific-dependent requirements of transforming growth factor-β signaling on neural stem cell proliferation and migration in vivo. |
| format | Article |
| id | doaj-art-e03e966e5fe347c2b6a4948acbb2142c |
| institution | DOAJ |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2026-03-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-e03e966e5fe347c2b6a4948acbb2142c2025-08-20T02:44:24ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582026-03-012131151116110.4103/NRR.NRR-D-24-00623Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migrationKierra WareJoshua PeterLucas McClainYu LuoAdult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of transforming growth factor-β signaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo, we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-β signaling in neural stem cells in (mGFAPcre-ALK5fl/fl-Ai9) or immature neuroblasts in (DCXcreERT2-ALK5fl/fl-Ai9). Our data showed that exogenous transforming growth factor-β treatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration. These effects were abolished in activin-like kinase 5 (ALK5) knockout primary neural stem cells. Consistent with this, inhibition of transforming growth factor-β signaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells. Interestingly, deletion of transforming growth factor-β receptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice, while abolishment of transforming growth factor-β signaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus. In summary, our data supports a dual role of transforming growth factor-β signaling in the proliferation and migration of neural stem cells in vitro. Moreover, our data provides novel insights on cell type–specific-dependent requirements of transforming growth factor-β signaling on neural stem cell proliferation and migration in vivo.https://journals.lww.com/10.4103/NRR.NRR-D-24-00623adult neurogenesisdoublecortinhippocampusmigrationneural stem cellsproliferationtransforming growth factor-β |
| spellingShingle | Kierra Ware Joshua Peter Lucas McClain Yu Luo Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration Neural Regeneration Research adult neurogenesis doublecortin hippocampus migration neural stem cells proliferation transforming growth factor-β |
| title | Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration |
| title_full | Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration |
| title_fullStr | Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration |
| title_full_unstemmed | Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration |
| title_short | Cell type–dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration |
| title_sort | cell type dependent role of transforming growth factor β signaling on postnatal neural stem cell proliferation and migration |
| topic | adult neurogenesis doublecortin hippocampus migration neural stem cells proliferation transforming growth factor-β |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00623 |
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