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Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1open access

Authors
Kim, NamsukLi, YanYu, RiKwon, Hyo-ShinSong, AnjiJun, Mi-HeeJeong, Jin-YoungLee, Ji HyunLim, Hyun-HoKim, Mi-JinKim, Jung-WoongOh, Won-Jong
Issue Date
Mar-2024
Publisher
eLife Sciences Publications
Keywords
axon guidance; Semaphorin 3E; Plexin-D1; Mtss1; basal ganglia development; Mouse
Citation
eLife, v.13
Journal Title
eLife
Volume
13
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/1160
DOI
10.7554/elife.96891
ISSN
2050-084X
Abstract
Axon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, metastasis suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons. Mtss1-knockout mice exhibited fewer striatonigral projections and irregular axonal routes, and these defects were recapitulated in Plxnd1- or Sema3e-knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding.
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연구본부 (신경·혈관 단위체 연구그룹)
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