title: Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling.
abstract: Neurogenesis in the adult hippocampus involves activation of quiescent neural stem cells (NSCs) to yield transiently amplifying NSCs, progenitors, and, ultimately, neurons that affect learning and memory. This process is tightly controlled by microenvironmental cues, although a few endogenous factors are known to regulate neuronal differentiation. Astrocytes have been implicated, but their role in juxtacrine (that is, cell-cell contact dependent) signaling in NSC niches has not been investigated. We found that ephrin-B2 presented from rodent hippocampal astrocytes regulated neurogenesis in vivo. Furthermore, clonal analysis in NSC fate-mapping studies revealed a previously unknown role for ephrin-B2 in instructing neuronal differentiation. In addition, ephrin-B2 signaling, transduced by EphB4 receptors on NSCs, activated β-catenin in vitro and in vivo independently of Wnt signaling and upregulated proneural transcription factors. Ephrin-B2(+) astrocytes therefore promote neuronal differentiation of adult NSCs through juxtacrine signaling, findings that advance our understanding of adult neurogenesis and may have future regenerative medicine implications.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, California, USA.
authors.forename: Randolph S
authors.initials: RS
authors.lastname: Ashton
authors.forename: Anthony
authors.initials: A
authors.lastname: Conway
authors.forename: Chinmay
authors.initials: C
authors.lastname: Pangarkar
authors.forename: Jamie
authors.initials: J
authors.lastname: Bergen
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Lim
authors.forename: Priya
authors.initials: P
authors.lastname: Shah
authors.forename: Mina
authors.initials: M
authors.lastname: Bissell
authors.forename: David V
authors.initials: DV
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D036388:Ephrin-B2 / Q000096:biosynthesis / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D036224:Receptor, EphB4 / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism
chemical_list: D036388:Ephrin-B2; D014157:Transcription Factors; D051176:beta Catenin; D036224:Receptor, EphB4