Date of Award

12-1983

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Professor J. Diamond

Abstract

The overall objective of this study was to investigate the physiological and trophic interactions that can occur between sensory nerves and their targets or end organs, specifically those between cutaneous mechanosensory axons and the epidermal Merkel cells. Previous work has shown that in salamander skin, the Merkel cell-neurite complex forms the morphological basis of the rapidly-adapting, low-threshold touch receptor (Cooper and Diamond, 1977; Parducz et al., 1977), while in mammalian species, it is associated with slowly-adapting mechanoreceptors. The present investigation has been carried out using Xenopus frogs (Xenopus laevis), in which the Merkel cells are located around the visible openings of the cutaneous gland ducts. A voltage-controlled mechanical stimulator of 10 μm tip diameter was used to compare the mechanosensory thresholds when the stimulator was applied directly over the gland openings ("on" locations) to those when the stimulator was located between the openings. The most sensitive points were always the "on" ones, and the results indicated that these represented a single population of rapidly-adapting, low-threshold touch receptors. Therefore, the locations of these mechanoreceptors coincided with the positions of the epidermal Merkel cell-neurite complexes, suggesting the latter have a mechanosensory function in Xenopus laevis.

An attempt was made to clarify the role of the Merkel cell in the mechanosensory process and in the trophic interactions believed to take place between the Merkel cells and the sensory nerves; this was done by following the development of mechanosensitivity when sensory nerves grow into nerve-free skin and observing whether there was any correlation with the appearance of the morphological features characteristic of the Merkel cell-neurite complex. These studies involved monitoring of the reinnervation of denervated skin, and the innervation of new skin that had regenerated in place of a portion previously excised. Merkel cells were shown to be present in both situations by using the fluorescent dye quinacrine as a marker for the Merkel cells and by EM examination. The development and maintenance of the Merkel cells seemed to be independent of nerves; they survived denervation, and they appeared in regenerated skin even in a totally denervated limb. Ingrowing sensory nerves eventually contacted these Merkel cells, which thus act as targets for these nerves. Preliminary results suggest that recovery of discrete low-threshold touch spots requires that contacts occur between the nerve endings and the Merkel cells. The mechanosensitivity develops gradually, however, concomitant with the gradual maturation of the Merkel cell-neurite complexes.

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