Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β)

Teclise Ng, Catherine Hong Huan Hor, Benjamin Chew, Jing Zhao, Zhong Zhong, Jae Ryun Ryu*, Eyleen L.K. Goh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Proper positioning of neurons is fundamental for brain functions. However, little is known on how adult-born neurons generated in the hilar side of hippocampal dentate gyrus migrate into the granular cell layer. Because class 3 Semaphorins (Sema3) are involved in dendritic growth of these newborn neurons, we examined whether they are essential for cell positioning. We disrupted Sema3 signaling by silencing neuropilin 1 (NRP1) or 2 (NRP2), the main receptors for Sema3A and Sema3F, in neural progenitors of adult mouse dentate gyrus. Silencing of NRP2, but not NRP1, affected cell positioning of adult newborn neurons. Glycogen synthase kinase-3β (GSK3β) knockdown phenocopied this NRP2 silencing-mediated cell positioning defect, but did not affect dendritic growth. Furthermore, GSK3β is activated upon stimulation with Sema3F, and GSK3β overexpression rescued the cell positioning phenotypes seen in NRP2-deficient neurons. These results point to a new role for NRP2 in the positioning of neurons during adult hippocampal neurogenesis, acting via the GSK3β signaling pathway.
Original languageEnglish
Pages (from-to)25088-25095
Number of pages8
JournalJournal of Biological Chemistry
Volume291
Issue number48
Early online date29 Sep 2016
DOIs
Publication statusPublished - 25 Nov 2016

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