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.

DOI: 10.1038/nn.3212

Extracted Key Phrases

0100200300201220132014201520162017
Citations per Year

765 Citations

Semantic Scholar estimates that this publication has 765 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Ashton2012AstrocytesRA, title={Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling}, author={Randolph Scott Ashton and Anthony Conway and Chinmay Pangarkar and Jamie Bergen and Kwang-il Lim and Priya S. Shah and Mina J. Bissell and David V. Schaffer}, booktitle={Nature Neuroscience}, year={2012} }