In the present study, the normal development of papillary ridges was studied in the volar pads of both fore and hindpaws of the opossum, Monodelphis domesticus. At birth, the developmental state of the opossum's paws is equivalent to that of a six-week human embryo. The development of papillary ridges in the opossum occurs entirely postnatally and the hindpaw lags behind the forepaw by at least four days in most developmental parameters. Papillary ridge formation is preceded by four events: skin innervation, Merkel cell differentiation, mesenchymal condensation, and epidermal proliferation. The apical pads at the tips of the digits and the interdigital pads between the heads of the metacarpals (or metatarsals) have a unique pattern of innervation and mesenchymal content as compared to the non-pad skin. Each pad is innervated by a prominent nerve trunk and axons ascend towards the epidermis providing a density of innervation that exceeds that in the non-pad epidermis. Merkel cells are absent in non-pad epidermis but present in the pads prior to the onset of formation of papillary ridges. A loose aggregation of mesenchyme forms the core of the pads and the superficial dermis is more cellular in the pads as compared to the equivalent dermis in surrounding non-pad skin. Developing papillary ridges always contained Merkel cell-axon complexes. Merkel cell axon complexes serve as the anatomical substrate of slowly adapting (SA) mechanoreceptors. The presence of these complexes during early skin differentiation is consistent with the use of the opossum's forepaw in climbing to the nipple, but also suggests other possible functions. We hypothesize that the nervous system might play a role in the timing or patterning of the formation of papillary ridges.

In order to test the hypothesis that the nervous system is an important determinant of skin differentiation, deletions of the left lumbosacral dorsal root ganglia (DRGs), the sources of cutaneous afferents to the left hindpaw, were performed on opossum pups at day 1 when hindpaws have just begun to be innervated. At birth, each lumbosacral DRG measures about 200 microns rostrocaudally and a deletion measuring 1 mm would span 4-5 DRGs. Following survival periods of 5-24 days, serial sections through the trunk documented partial left lumbosacral DRG deletion and a variable degree of spinal cord destruction. The blood supply to the trunk and hindpaws was preserved. Bilateral enlargement of residual DRGs was observed and regenerating skin at the site of the deletion was hyperplastic and hyperinnervated. The skin of the plantar pads of the hindpaws was studied following the neuralectomies. Statistically significant differences were observed between the left (experimental) and right (control) hindpaws. The density of innervation of the left hindpaw was reduced compared to the right hindpaw, development of papillary ridges was retarded by 3-4 days, and non-innervated Merkel cells were hypogranulated. This period of delay in ridge development is probably a reflection of the expansion of residual DRGs into the peripheral domains of deleted DRGs. The present study confirms a role for afferent nerves in the timing of cutaneous differentiation and a mutual trophic dependence between cutaneous nerves and Merkel cells in the epidermis.