Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β).
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.
From the Programme in Neuroscience and Behavioral Disorder and.
Teclise
T
Ng
Neuroscience Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore.|the Department of Research, National Neuroscience Institute, Singapore 308433, Singapore.
Catherine H H
CH
Hor
From the Programme in Neuroscience and Behavioral Disorder and.
Benjamin
B
Chew
GlaxoSmithKline (China) R&D Co., Ltd., Shanghai 201203, China.
Jing
J
Zhao
GlaxoSmithKline (China) R&D Co., Ltd., Shanghai 201203, China.
Zhong
Z
Zhong
From the Programme in Neuroscience and Behavioral Disorder and jaeryunryu@gmail.com.
Jae Ryun
JR
Ryu
From the Programme in Neuroscience and Behavioral Disorder and eyleen.goh@duke-nus.edu.sg.|Neuroscience Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore.|the Department of Research, National Neuroscience Institute, Singapore 308433, Singapore.|the Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore, and.|the KK Research Center, KK Women's and Children's Hospital, Singapore 229899, Singapore.
Eyleen L K
EL
Goh
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D039943:Neuropilin-2 / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C488217:Sema3a protein, mouse; C491229:Sema3f protein, mouse; D040121:Semaphorin-3A; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse
adult-born neurons; cell migration; cell positioning; glycogen synthase kinase 3 (GSK-3); hippocampus; neurogenesis; neuron; neuropilin
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