title: BMP signaling in astrocytes downregulates EGFR to modulate survival and maturation.
abstract: Astrocytes constitute a major cell population in the brain with a myriad of essential functions, yet we know remarkably little about the signaling pathways and mechanisms that direct astrocyte maturation. To explore the signals regulating astrocyte development, we prospectively purified and cultured immature postnatal rodent astrocytes. We identified fibroblast growth factors (FGFs) and bone morphogenetic proteins (BMPs) as robust trophic factors for immature astrocytes. We showed that astrocytes respond directly to BMPs via phosphorylation of the smad1/5/8 pathway. In vitro, BMP signaling promoted immature astrocytes to adopt multiple characteristics of mature astrocytes, including a more process-bearing morphology, aquaporin-4 (AQP4) and S100β immunoreactivity, limited proliferation, and strong downregulation of epidermal growth factor receptor (EGFR). In vivo, activation of the smad1/5/8 pathway in astrocytes was seen during early postnatal development, but inhibition of astrocyte proliferation was not observed. These insights can aid in the further dissection of the mechanisms and pathways controlling astrocyte biology and development.
authors.affiliation: Stanford University School of Medicine, Department of Neurobiology, Stanford, California, United States of America.
authors.forename: Anja R
authors.initials: AR
authors.lastname: Scholze
authors.affiliation: Institute of Molecular and Cell Biology, A *Star, Singapore, Singapore.
authors.forename: Lynette C
authors.initials: LC
authors.lastname: Foo
authors.affiliation: Stanford University School of Medicine, Department of Neurobiology, Stanford, California, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Mulinyawe
authors.affiliation: Stanford University School of Medicine, Department of Neurobiology, Stanford, California, United States of America.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins; C483803:Egfr protein, rat; D066246:ErbB Receptors