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Inactivating Celsr2 promotes motor axon fasciculation and regeneration in mouse and human

journal contribution
submitted on 2024-04-24, 05:30 and posted on 2024-04-24, 05:31 authored by Quan Wen, Huandi Weng, Tao Liu, Lingtai Yu, Tianyun Zhao, Jingwen Qin, Si Li, Qingfeng Wu, Fadel Tissir, Yibo Qu, Libing Zhou

Understanding new modulators of axon regeneration is central to neural repair. Our previous work demonstrated critical roles of atypical cadherin Celsr2 during neural development, including cilia organization, neuron migration and axon navigation. Here, we address its role in axon regeneration.

We show that Celsr2 is highly expressed in both mouse and human spinal motor neurons. Celsr2 knockout promotes axon regeneration and fasciculation in mouse cultured spinal explants. Similarly, cultured Celsr2 mutant motor neurons extend longer neurites and larger growth cones, with increased expression of end-binding protein 3 and higher potassium-induced calcium influx. Mice with Celsr2 conditional knockout in spinal motor neurons do not exhibit any behavioural deficits; however, after branchial plexus injury, axon regeneration and functional forelimb locomotor recovery are significantly improved. Similarly, knockdown of CELSR2 using shRNA interference in cultured human spinal motor explants and motor neurons increases axonal fasciculation and growth. In mouse adult spinal cord after root avulsion, in mouse embryonic spinal cords, and in cultured human motor neurons, Celsr2 downregulation is accompanied by increased levels of GTP-bound Rac1 and Cdc42, and of JNK and c-Jun.

In conclusion, Celsr2 negatively regulates motor axon regeneration and is a potential target to improve neural repair.

Other Information

Published in: Brain
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  • English


Oxford University Press

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU

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