TY - JOUR TI - Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice AU - Zhang, Hongsheng AU - Sathyamurthy, Anupama AU - Liu, Fang AU - Li, Lei AU - Zhang, Lei AU - Dong, Zhaoqi AU - Cui, Wanpeng AU - Sun, Xiangdong AU - Zhao, Kai AU - Wang, Hongsheng AU - Ho, Hsin-Yi Henry AU - Xiong, Wen-Cheng AU - Mei, Lin A2 - Bronner, Marianne E A2 - Shen, Kang VL - 8 PY - 2019 DA - 2019/07/03 SP - e45303 C1 - eLife 2019;8:e45303 DO - 10.7554/eLife.45303 UR - https://doi.org/10.7554/eLife.45303 AB - Adult neurogenesis in the hippocampus may represent a form of plasticity in brain functions including mood, learning and memory. However, mechanisms underlying neural stem/progenitor cells (NSPCs) proliferation are not well understood. We found that Agrin, a factor critical for neuromuscular junction formation, is elevated in the hippocampus of mice that are stimulated by enriched environment (EE). Genetic deletion of the Agrn gene in excitatory neurons decreases NSPCs proliferation and increases depressive-like behavior. Low-density lipoprotein receptor-related protein 4 (Lrp4), a receptor for Agrin, is expressed in hippocampal NSPCs and its mutation blocked basal as well as EE-induced NSPCs proliferation and maturation of newborn neurons. Finally, we show that Lrp4 interacts with and activates receptor tyrosine kinase-like orphan receptor 2 (Ror2); and Ror2 mutation impairs NSPCs proliferation. Together, these observations identify a role of Agrin-Lrp4-Ror2 signaling for adult neurogenesis, uncovering previously unexpected functions of Agrin and Lrp4 in the brain. KW - adult neurogenesis KW - enriched environment KW - depressive-like behavior JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -