Biology subjects

Udina, E.

Publications and source records attributed to Udina, E..

4 recordsLinked to original sources

bioRxiv2026

Outgrowth of Mouse Sensory Neurons is not Mediated by Regeneration Associated Genes in Early Postnatal Stages

Peripheral neurons exhibit robust regeneration after nerve injury in adulthood; a process linked to the activation of regeneration-associated genes (RAGs). However, the mechanisms underlying nerve regeneration during early postnatal development remain poorly understood. In a previous work, we observed that motoneurons axotomized at early postnatal stages regenerate without overexpressing RAGs, contrasting with the expected RAG activation observed in postnatal day 30 (P30) mice. To determine whether this phenomenon extends to sensory neurones, we investigated two paradigmatic dorsal root ganglia populations: proprioceptive (PV) and nociceptive (TrpV1) neurones, which exhibit distinct regenerative capacities in adult mice. Following sciatic nerve crush injury at P4, P10, and P30, both neuronal subtypes demonstrated robust axonal regeneration across all postnatal stages, with nociceptors exhibiting significantly superior regeneration compared to proprioceptors. Remarkably, no substantial neuronal death was observed at any developmental timepoint. However, RNA sequencing revealed that P4 and P10 sensory neurones failed to upregulate RAGs following injury, whereas P30 neurones exhibited the expected pro-regenerative transcriptional programme. Pathway enrichment analysis confirmed that classical regeneration-associated signalling pathways were activated exclusively in young adults, whilst developmental and inflammatory pathways predominated in early postnatal stages. Using the conditioning lesion paradigm in primary dorsal root ganglia cultures, we demonstrated that only P30 neurones exhibited enhanced neurite outgrowth following conditioning lesion, whilst P4 and P10 neurones showed no conditioning effect or reduced outgrowth, respectively. These findings indicate that early postnatal sensory neurones possess intrinsic growth capacity independent of RAG activation, suggesting fundamentally distinct regenerative mechanisms across developmental stages.

neuroscience↗

bioRxiv2025

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

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.

neuroscience↗

bioRxiv2025

Assessment of Motoneuronal Regeneration and Wallerian Degeneration Following Axotomy in Postnatal Mice

Nerve injuries during early postnatal stages results in markedly different outcomes compared to adult injury, with significant motoneuronal death masking potential regenerative capacity. This study systematically evaluated motoneuronal survival, axonal regeneration, and Wallerian degeneration following peripheral nerve injury at distinct postnatal stages (P4, P10, and P30) in mice. Using ChAT-Cre/Ai9(RCL-tdT) and ChAT-Cre/RiboTag transgenic models, we assessed both histological and transcriptomic responses after sciatic nerve lesions. Injury at P4 induced substantial motoneuron death (1150%), whilst P10 and P30 animals showed minimal neuronal loss. However, when correcting for neuronal survival, P4 mice demonstrated the highest regenerative capacity, with surviving neurons achieving 100% axonal regeneration. Motoneuron-specific translatome analysis revealed that P30 animals activated a robust regeneration-associated gene (RAG) programme, including classical markers such as Atf3, Gap43, and Ngfr. In contrast, P4 neurons showed minimal RAG upregulation, suggesting they retain an intrinsic growth state that facilitates regeneration without requiring transcriptional reprogramming. P10 animals exhibited a transitional phenotype with impaired RAG activation and reduced regenerative capacity. Wallerian degeneration proceeded efficiently across all developmental stages, with age-specific differences in myelin clearance kinetics and macrophage recruitment. Transcriptomic analysis confirmed consistent downregulation of myelination programmes and upregulation of pro-regenerative markers following injury, regardless of age. These findings indicate that regenerative capacity is primarily determined by the intrinsic growth state of motoneurons rather than extrinsic factors. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/691768v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@9079b4org.highwire.dtl.DTLVardef@12640b7org.highwire.dtl.DTLVardef@62e763org.highwire.dtl.DTLVardef@1453180_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Neuron-specific RNA-sequencing reveals different regeneration mechanisms in peripheral neurons after nerve injury

Peripheral neurons are heterogeneous and functionally diverse, but all share the capability to switch to a pro-regenerative state after nerve injury. Despite the assumption that the injury response is similar among neuronal subtypes, functional recovery may differ. Understanding the distinct intrinsic regenerative properties between neurons may help to improve the quality of regeneration, prioritizing the growth of axon subpopulations to their targets. Here, we present a comparative analysis of regeneration across four key peripheral neuron populations: motoneurons, proprioceptors, cutaneous mechanoreceptors, and nociceptors. Using Cre/Ai9 mice that allow fluorescent labelling of neuronal subtypes, we found that nociceptors showed the greater regeneration after a sciatic crush, followed by motoneurons, mechanoreceptors and, finally, proprioceptors. By breeding these Cre mice with Ribotag mice, we isolated specific translatomes and defined the regenerative response of these neuronal subtypes after axotomy. Only 20% of the regulated genes were common, revealing a diverse response to injury among neurons, which was also supported by the differential influence of neurotrophins among neuron subtypes. Among differentially regulated genes, we proposed MED12 as a specific regulator of the regeneration of proprioceptors. Altogether, we demonstrate that the intrinsic regenerative capacity differs between peripheral neuron subtypes, opening the door to selectively modulate these responses.

neuroscience↗