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dc.contributor.authorSelvaraj, P.
dc.contributor.authorXiao, L.
dc.contributor.authorLee, C.
dc.date.accessioned2019-07-15T16:17:00Z
dc.date.available2019-07-15T16:17:00Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85002141995&doi=10.1002%2fstem.2511&partnerID=40&md5=a467b73bd4330c2c51dbe53a3a7d2a02
dc.identifier.urihttp://hdl.handle.net/10713/10045
dc.description.abstractEmbryonic 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‐α1, 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 β‐catenin. NF‐α1 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‐α1‐knockout mice showed decreased astrocyte numbers compared to wild‐type mice, which was rescued by treatment with NF‐α1. In vivo, immunocytochemistry of brain sections and Western blot analysis of neocortex of mice showed a gradual increase of NF‐α1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF‐α1‐Knockout mice showed ∼49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF‐α1 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. Copyright 2016 AlphaMed Pressen_US
dc.description.sponsorshipThis research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, USA.en_US
dc.description.urihttps://www.doi.org/10.1002/stem.2511en_US
dc.language.isoen_USen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofStem Cells
dc.subjectAstrocytesen_US
dc.subjectCarboxypeptidase Een_US
dc.subjectNeurotrophic factor‐α1en_US
dc.subjectStem cellen_US
dc.subjectWnt pathwayen_US
dc.titleNeurotrophic Factor‐α1: A Key Wnt‐β‐Catenin Dependent Anti‐Proliferation Factor and ERK‐Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopmenten_US
dc.typeArticleen_US
dc.identifier.doi10.1002/stem.2511
dc.identifier.pmid27709799


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