The control of epidermal mitotic activity in the mouse

Abstract

A study has been made of the abnormally high mitotic activity seen in mouse epidermis adjacent to a wound. Such activity is in the form of a gradient, no more than about 1 mm long, with the highest mitotic rate adjacent to the cut edge. It is shown that this gradient is not due to differential damage or to the effects of local hyperaemia. When the hypodermis and dermis are wounded from below, the overlying undamaged epidermis does not react by mitosis. Such a wound includes damage to the panniculus carnosus, the hair follicles and the sebaceous glands. It also involves hyperaemia and an invasion of leucocytes. It therefore appears that damage to the epidermis itself is necessary before an epidermal reaction can develop. Such a reaction could be due either to the secretion by the damaged epidermis of a mitosis stimulating ‘wound hormone' or to the local elimination of a normally present epidermal mitotic inhibitor. It was observed that when one side of the ear is wounded high mitotic activity develops in the opposite undamaged epidermis, which is less than 1 mm distant. In further experiments it was found that the greatest reaction in a sheet of undamaged ear epidermis is opposite the centre of an area from which the epidermis has been removed altogether. Since the area from which the epidermis was removed was 3 mm square, it is obvious that an epidermal ‘wound hormone' could not have been present in effective concentration in the central region, but the absence of an inhibitor which would normally have been present could explain the result obtained. It is therefore concluded that the gradient of epidermal mitotic activity adjacent to a wound may be inversely proportional to a gradient of mitotic inhibitor, which may cease to be produced within damaged cells and which may also diffuse away into the cavity of a wound. The question of the possible presence within the adult mouse of a complex of growth-controlling tissue-specific inhibitors is discussed, and evidence for its existence is reviewed.