Graduate School of Frontier Biosciences, Osaka University

Japanese

Netrin-4 Regulates Thalamocortical Axon Branching in an Activity-Dependent Fashion

Journal Proc Natl Acad Sci USA 111, 15226-15231 (2014)
Authors Hayano Y. (1, 3), Sasaki K. (1), Ohmura N. (2), Takemoto M. (1), Maeda Y. (1), Yamashita T. (3), Hata Y. (2), Kitada K. (4), Yamamoto N. (1)

  1. Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
  2. Division of Integrative Bioscience, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Sciences, 86 Nishicho Yonago, 683-8503, Japan
  3. Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
  4. Laboratory of Mammalian Genetics, Division of Genome Dynamics, Creative Research Initiative ''Sousei'', Hokkaido University, North 10 West 8, Kita-ku, Sapporo 060-0810, Japan
Title Netrin-4 Regulates Thalamocortical Axon Branching in an Activity-Dependent Fashion
PubMed 25288737
Laboratory Cellular and Molecular Neurobiology Group 〈Prof. Yamamoto〉
Description 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 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, 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.

During development, thalamocortical axons form connections with cortical neurons. When neuronal activity is increased by sensory stimulation (right), Netrin-4 is more expressed in cortical cells. As Netrin-4 promotes axon branching, thalamocortical axons form more branches. Thus, neuronal activity-dependent Netrin-4 expression regulates neuronal circuits in the developing neocortex.

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