title: Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion.
abstract: Axon branching is remodeled by sensory-evoked and spontaneous neuronal activity. However, the underlying molecular mechanism is largely unknown. Here, we demonstrate that the netrin family member netrin-4 (NTN4) contributes to activity-dependent thalamocortical (TC) axon branching. In the postnatal developmental stages of rodents, ntn4 expression was abundant in and around the TC recipient layers of sensory cortices. Neuronal activity dramatically altered the ntn4 expression level in the cortex in vitro and in vivo. TC axon branching was promoted by exogenous NTN4 and suppressed by depletion of the endogenous protein. Moreover, unc-5 homolog B (Unc5B), which strongly bound to NTN4, was expressed in the sensory thalamus, and knockdown of Unc5B in thalamic cells markedly reduced TC axon branching. These results suggest that NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression.
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; and.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Hayano
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;
authors.forename: Kensuke
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Division of Integrative Bioscience, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Sciences, 86 Nishicho, Yonago 683-8503, Japan;
authors.forename: Nami
authors.initials: N
authors.lastname: Ohmura
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;
authors.forename: Makoto
authors.initials: M
authors.lastname: Takemoto
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;
authors.forename: Yurie
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; and.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Division of Integrative Bioscience, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Sciences, 86 Nishicho, Yonago 683-8503, Japan;
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hata
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kitada
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; nobuhiko@fbs.osaka-u.ac.jp.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D018920:Coculture Techniques; D018274:Electroporation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000502:physiology*; D000075386:Netrin Receptors; D000075385:Netrins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013788:Thalamus / Q000378:metabolism / Q000502:physiology*; D014793:Visual Cortex / Q000378:metabolism
chemical_list: C498815:NTN4 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D000075385:Netrins; C416214:Ntn4 protein, mouse; D011956:Receptors, Cell Surface; C532445:UNC5B protein, human
keywords: axon guidance; development; neocortex; neuronal wiring