title: Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization.
abstract: Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both in vitro and in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.
authors.affiliation: Institute of Neuroscience and Key State Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Lei
authors.forename: Shi-Ge
authors.initials: SG
authors.lastname: Xing
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Deng
authors.forename: Xiang-Chun
authors.initials: XC
authors.lastname: Ju
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Jiang
authors.forename: Zhen-Ge
authors.initials: ZG
authors.lastname: Luo
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000502:physiology*; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011137:Polystyrenes / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D019012:Integrin beta1; D007797:Laminin; D011137:Polystyrenes; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases