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bioRxiv · 10.64898/2025.12.13.691790

Peripheral regeneration of Aβ low-threshold mechanoreceptors is limited despite activation of regenerative transcriptional pathways

Bolivar, S.·Martinez-Mateu, N.·Ovelleiro, D.·Udina, E.
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Abstract

Peripheral neurons can regenerate after nerve injury, yet functional recovery is often incomplete due to non-specific or incomplete target reinnervation. Among sensory neuron subtypes, A{beta} low-threshold mechanoreceptors (A{beta}-LTMRs) mediate discriminative touch, a modality often incompletely restored after nerve injury. However, the mechanisms governing A{beta}-LTMR regeneration remain largely unexplored. Here, we characterised the anatomical and transcriptional features of A{beta}-LTMRs regeneration after nerve injury. We assessed the extent of axonal regeneration after sciatic nerve crush and the preferential regeneration following femoral nerve transection using Calb1-Cre/tdTomato reporter mice. In both models, regeneration was incomplete, failing to reach control values. Moreover, A{beta}-LTMRs preferentially reinnervated cutaneous rather than muscle pathways. To define the molecular program underlying this response, we performed ribosome-bound RNA sequencing from Calb1-Cre/Ribotag mice 7 days after nerve crush. A{beta}-LTMRs upregulated canonical regeneration-associated genes, including Atf3, Sprr1a, Gal, and Gap43. Comparison with published RNA-seq datasets from other sensory neuron populations revealed only modest overlap, indicating that the core injury response shared between neurons is accompanied by a neuron subtype-specific programme. Together, these findings define the regenerative profile of A{beta}-LTMRs across anatomical and transcriptomic levels, revealing the limited regenerative capacity of this neuron subpopulation despite robust activation of classical regeneration-associated genes.

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Bolivar, S., Martinez-Mateu, N., Ovelleiro, D., Udina, E.. 2025-12-16. Peripheral regeneration of Aβ low-threshold mechanoreceptors is limited despite activation of regenerative transcriptional pathways. https://doi.org/10.64898/2025.12.13.691790

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