| First Author | Selvaraj P | Year | 2017 |
| Journal | Stem Cells | Volume | 35 |
| Issue | 3 | Pages | 557-571 |
| PubMed ID | 27709799 | Mgi Jnum | J:237213 |
| Mgi Id | MGI:5811703 | Doi | 10.1002/stem.2511 |
| Citation | Selvaraj P, et al. (2017) Neurotrophic Factor-alpha1: A Key Wnt-beta-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment. Stem Cells 35(3):557-571 |
| abstractText | Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells (NSCs) followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF-alpha1, which inhibits proliferation and promotes differentiation of NSC/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing beta-catenin. NF-alpha1 induced differentiation of NSCs to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2-Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF-alpha1-knockout mice showed decreased astrocyte numbers compared to wild-type mice, which was rescued by treatment with NF-alpha1. In vivo, immunocytochemistry of brain sections and Western blot analysis of neocortex of mice showed a gradual increase of NF-alpha1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF-alpha1-Knockout mice showed approximately 49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF-alpha1 is critical for regulating antiproliferation and cell fate determination, through differentiating embryonic stem cells to GFAP-positive astrocytes for normal neurodevelopment. Stem Cells 2017;35:557-571. |
