Cell type-dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration
Kierra Ware1
Joshua Peter1
Lucas McClain1
Yu Luo2
1.Department of Molecular and Cellular Biosciences,University of Cincinnati,Cincinnati,OH,USA2.Department of Molecular and Cellular Biosciences,University of Cincinnati,Cincinnati,OH,USA;Neuroscience Graduate Program,University of Cincinnati,Cincinnati,OH,USA;Division of Immunobiology,Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine,Cincinnati,OH,USA
摘要：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.
机标关键词：stemgrowthcellrolefactor-migrationneuralpostnatal
论文发表日期：2026-03-30
在线出版日期：2026-03-18（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1151-1161 )
英文信息