Aβ-LTMRs exhibit absent or limited sprouting into denervated skin after peripheral nerve injury. A, Schematic of characteristic lanceolate endings of Aβ RA-LTMR labeled in Split^Cre-Rosa26^LSLtdTomato mice (left). Modified from Abraira and Ginty (2013). Whole-mount immunostaining of plantar hairy skin from Split^Cre-Rosa26^LSLtdTomato mice for tdTomato (red) and K17 (blue, hair follicle marker). Arrow in inset indicates lanceolate nerve ending (middle). Immunostaining for tdTomato (red) in FB retrogradely labeled plantar hairy skin-innervating neurons (blue) in lumbar DRGs from Split^Cre-Rosa26^LSLtdTomato. Arrow indicates retrogradely labeled FB/tdTomato doubly positive neurons (right). Scale bar, 100 μm. B, In vivo electrophysiological recordings in the hindpaw from Split^Cre-Rosa26^LSLtdTomato mice (n = 4). (a) Schematic showing receptive fields (RF) for all 10 individual neurons used for recording. Red dots represent neurons for which both mechanically stimulation response and conduction velocity (CV) were measured, and blue dots represent neurons for which only CV was measured. (b) A quantitative graph of CV of tdtomato⁺ neurons. (c) Representative in vivo electrophysiological recordings from an Aβ RA-LTMR in response to 80 mN mechanical stimulation with a 0.5 mm diameter tipped probe. C–C```, In Split<sup>Cre</sup>-Rosa26<sup>LSLtdTomato</sup> mice, whole mount immunostaining for tdTomato (red) in the ipsilateral plantar hairy skin of the hindpaw before (C) and 1(C`), 4(C``), and 8(C```) weeks after SNI. Arrow in inset indicates lanceolate nerve ending. Scale bar, 100 μm. D, Quantification of Split^Cre Rosa26^LSL-tdTomato (n = 5–7) nerve density fraction in the contralateral (black) and ipsilateral (red) hindpaw plantar hairy skin at the indicated times after SNI. E, Quantification of Split^Cre-Rosa26^LSLtdTomato (Aβ RA-fiber, n = 5–7) tdTomato⁺ nerve fiber ending density in the contralateral (black) and ipsilateral (red) plantar hairy skin of hindpaw at the indicated times after SNI. F, Whole-mount immunostaining of plantar hairy skin from TrkC^tdTomato mice for tdTomato (red) and K8 (green, Merkel cell). Insets show higher magnification views of the areas indicated by dashed boxes. Arrow in inset (a) indicates K8⁺ Merkel cells cluster and associated Aβ SA1 LTMR ending in plantar hairy skin. Inset (b) shows TrkC^tdTomato circumferential nerve ending, presumably a field LTMR. Scale bar, 100 μm. Images of tissues used in Figure 4F have been presented previously (Jeon et al., 2021). G–G```,H, In TrkC<sup>tdTomato</sup> mice, whole mount immunostaining for tdTomato (red) in the ipsilateral plantar hairy skin of the hindpaw before (G) and 1(G`), 4(G``), and 8(G```) weeks after SNI. Arrows indicate TrkC^tdTomato+ fibers. In the ipsilateral hindpaw plantar hairy skin, arrows indicate TrkC^tdTomato circumferential nerve ending (H). Scale bar, 100 μm. I, Quantification of TrkC^tdTomato (n = 5–8) nerve density fraction in the contralateral (black) and ipsilateral (red) hindpaw plantar hairy skin at the indicated times after SNI. J, In TrkC^CreER-Rosa26^LSL-EYFP mice with treated with 0.1 mg 4-HT at P5, whole mount immunostaining for tdTomato (red) in the ipsilateral plantar hairy skin of the hindpaw at 8 weeks after SNI. Insets indicate TrkC^tdTomato+ fibers. Scale bar, 100 μm. K, Double immunostaining for TrkC;tdTomato⁺ (red) and NF-H⁺ (green) in hindpaw 8 weeks after SNI. Subpanels a–d indicate IMARIS 3D rendered images. Subpanels b and d show colocalization (yellow) of TrkC;tdTomato⁺ and NF-H⁺ staining. Scale bar, 20 μm. L, Quantification of the percentages of NF-H⁺ only and NF-H⁺ TrkC⁺ among total NF-H⁺ nerve fibers in contralateral and ipsilateral plantar hairy skin 8 weeks after SNI surgery (n = 5). M, Quantification of the percentages of TrkC⁺ only and TrkC⁺ NF-H⁺ among total TrkC⁺ nerve fibers in contralateral and ipsilateral plantar hairy skin 8 weeks after SNI surgery (n = 5). N,O, Correlation between percent TrkC⁺ NF-H⁺ double labeling and density of all TrkC⁺ nerve fibers in contralateral (N) and ipsilateral (O) plantar hairy skin 8 weeks after SNI surgery (n = 5). Data are presented as mean ± SEM. In panels D,E,I, (1) indicates overall p-value for difference between baseline and ipsilateral hindpaw s over time using one-way ANOVA. Results of Bonferroni post hoc correction shown as: ⁺p < 0.05; ⁺⁺p < 0.01; ⁺⁺⁺p < 0.001; ⁺⁺⁺⁺p < 0.0001. (2) Indicates overall p-value for difference between ipsilateral and contralateral paws over time using two-way ANOVA. Results of Bonferroni post hoc correction shown as: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. In panels K and L, overall p-value is from difference between ipsilateral and contralateral paws using two-way ANOVA. In panels N and O, correlation coefficient (r) and p-value from Pearson correlation; **p < 0.01, TrkC⁺ NF-H⁺ versus density of all TrkC⁺. Full statistical details can be found in Table 1.