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Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):E10206-E10215. doi: 10.1073/pnas.1704372114. Epub 2017 Nov 6.

let-7 miRNA controls CED-7 homotypic adhesion and EFF-1-mediated axonal self-fusion to restore touch sensation following injury.

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National Brain Research Centre, Manesar, Nainwal Mode, Gurgaon, Haryana 122051, India.
Bruker India Scientific Private Ltd, New Delhi 110019, India.
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400 005, India.
National Brain Research Centre, Manesar, Nainwal Mode, Gurgaon, Haryana 122051, India;
Wellcome Trust-Department of Biotechnology India Alliance, Banjara Hills, Hyderabad, Telangana 500034, India.


Neuronal injury often leads to devastating consequences such as loss of senses or locomotion. Restoration of function after injury relies on whether the injured axons can find their target cells. Although fusion between injured proximal axon and distal fragment has been observed in many organisms, its functional significance is not clear. Here, using Caenorhabditis elegans mechanosensory neurons, we address this question. Using two femtosecond lasers simultaneously, we could scan and sever posterior lateral microtubule neurons [posterior lateral microtubules (PLMs)] on both sides of the worm. We showed that axotomy of both PLMs leads to a dramatic loss of posterior touch sensation. During the regenerative phase, only axons that fuse to their distal counterparts contribute to functional recovery. Loss of let-7 miRNA promotes functional restoration in both larval and adult stages. In the L4 stage, loss of let-7 increases fusion events by increasing the mRNA level of one of the cell-recognition molecules, CED-7. The ability to establish cytoplasmic continuity between the proximal and distal ends declines with age. Loss of let-7 overcomes this barrier by promoting axonal transport and enrichment of the EFF-1 fusogen at the growing tip of cut processes. Our data reveal the functional property of a regenerating neuron.


axotomy; femtosecond laser; fusion; gentle touch; let-7

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