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Fig. 3. Diminished innervation of the skin in K14-BMP4 mice. Innervation of the
epidermis and upper dermis at comparable locations in the intervibrissal fur
in wild type and K14-BMP4 mice. Labels are similar to those in
Fig. 2. (A-D) Double-label
immunofluorescence with anti-CGRP (Cy3) and anti-PGP (Cy2). At 1 month, the
innervation to the epidermis appears comparable in wild type and K14-BMP4
mice. At 6 months, innervation in the K14-BMP4 mice has become reduced and
fragmented. However, most of the remaining innervation expresses CGRP-IR,
which may be more than in wild type. Yellow arrows indicate sites where axons
express CGRP IR. In contrast to wild type, in K14-BMP4 transgenics most
epidermal innervation seems to be supplied directly from the third tier of the
dermal plexus. Axon bundles at the epidermal-dermal border, indicative of the
fourth tier, are readily encountered in wild type. The fourth tier was rarely
detected in K14-BMP4 intervibrissal fur. A-D are all mice from CB6F1
background. (E-H) Comparison of the innervation to the epidermis and upper
dermis at comparable locations in the intervibrissal fur and in wild-type,
K14-BMP4 and K14-noggin mice as shown by double-label immunofluorescence with
anti-CGRP (Cy3) and anti-NF200 (Cy2). E,F are from a CB6F1 background; G,H are
from a Fvb background. Red arrows indicate axons labeled only with anti-CGRP,
green arrows labeled only with anti-NF200, yellow arrows labeled with both
anti-CGRP and anti-NF. Note the massive increase in CGRP-positive innervation
at all levels of the dermal plexus in the K14-noggin fur. In both wild-type
and K14-noggin mice, the third and fourth tiers of the dermal plexus contain
anti-CGRP labeled axons that are mostly NF200 negative (red arrows). Likewise,
the anti-CGRP labeled endings in the epidermis lack NF200-IR (red arrowheads).
A few axons in the third tier contain NF200 but most of the
CGRP-positive/NF200-positive axons are in the second tier. By contrast, in the
K14-BMP4 fur, most of the CGRP positive innervation at all levels co-expresses
NF200-IR. This includes an ending in the epidermis that co-expresses CGRP-IR
and NF200-IR (yellow arrowhead), which is never seen in the wild-type
epidermis.
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