TY - JOUR
T1 - Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β)
AU - Ng, Teclise
AU - Hor, Catherine Hong Huan
AU - Chew, Benjamin
AU - Zhao, Jing
AU - Zhong, Zhong
AU - Ryu, Jae Ryun
AU - Goh, Eyleen L.K.
N1 - This work was supported by Abbott Nutrition, the Academic Center of Excellence (ACE) research award from GlaxoSmithKline (GSK), and the National Research Foundation Singapore under its Competitive Research Program (Grant NRF 2008 NRF-CRP 002-082) (to E. L. K. G.). The authors declare that they have no conflicts of interest with the contents of this article.
PY - 2016/11/25
Y1 - 2016/11/25
N2 - 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.
AB - 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.
UR - http://europepmc.org/articles/PMC5122776
U2 - 10.1074/jbc.M116.755215
DO - 10.1074/jbc.M116.755215
M3 - Journal article
C2 - 27687730
SN - 0021-9258
VL - 291
SP - 25088
EP - 25095
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -
