Fig. 2. Hyperinnervation of the skin in postnatal and adult K14-noggin animals. Innervation of the epidermis and upper dermis at comparable locations in the intervibrissal fur (A-D) and at the mouth of vibrissal follicles (E,F) in wild-type and K14-noggin overexpressing mice (K14-Nog) as shown by double-label immunofluorescence with anti-CGRP revealed with Cy3 and anti-PGP revealed with Cy2. e, epidermis; f, hair follicle; ^*, the mouth of a whisker follicle. The broken line indicates the border between the epidermis and dermis. Green arrowheads indicate examples of FNEs in the epidermis that are labeled only with anti-PGP. Yellow arrowheads indicate examples of epidermal FNEs that also label with anti-CGRP. Note that the epidermis of the K14-Nog mice contains far more FNEs with and without CGRP-IR. Broad arrowheads with numbers 2, 3 and 4 indicate regions of the second, third and fourth tiers of the dermal plexus respectively. In K14-Nog mice, the bundles of axons that compose the fourth tier are much larger and occupy a greater proportion of the epidermal-dermal border. In wild type, axons with CGRP-IR (yellow arrows) are mostly restricted to the second and third tiers. In K14-Nog, numerous axons with CGRP-IR are also located in the fourth tier. However, at E15 there are no detectable differences in PGP immunostaining between transgenic and control mice (G,H). Panels A-H are all mice from an Fvb background. (I-L) Quantification of the innervation to the epidermis and upper dermis in K14-Nog mice. The quantitative analyses were carried out on five sections for each mouse and the mean for each parameter obtained. Mean±s.e.m. of three mice for each genotype are shown (^*P<0.05; ^**P<0.005; ^***P<0.0005).