This study was undertaken to determine the effects of beryllium nitrate on regeneration in the tail of Rana Pipiens larvae. The tails were amputated approximately 3 rom from the tips. Some were then treated with different concentrations of beryllium nitrate (0.5 N, 0.7 N, and 1.0 N). Normal regeneration of untreated amputated tails was fulfilled in an orderly manner. In the animals treated with beryllium nitrate, general tissue regeneration was inhibited. Considerable degeneration was observed in all tissues of the tail stumps. Holfever, the elastic lamella of the notochordal sheath was stimulated to stretch, oftentimes breaking the continuity of the fibrous lamella. The elastic layer appeared highly ravelled within the degenerated tissues of the tail, and, in some cases, extended for 3 to 4 inches from the tail stump due to a break in the covering epithelium.

Tissue regeneration in salamanders is a robust process that is not easily interrupted or altered. Therefore, inhibiting regeneration provides a means to interrogate the underlying cellular and molecular mechanisms regulating this complex event. Here we show that application of a relatively low concentration of beryllium nitrate solution (100mM) causes a delay in skin regeneration and severely alters normal limb regeneration. We provide evidence showing a beryllium-induced reduction in dermal fibroblast migration in vivo and in vitro. We link this phenomenon to delayed regeneration of the skin and abnormal blastema formation resulting in limb patterning defects during regeneration. Though our results show a slight reduction in fibroblast proliferation during the early stages of limb regeneration, we attribute this to an overall reduction in fibroblast presence at the site of injury. Keratinocytes appeared unresponsive to beryllium treatment with the rates of re-epithelialization and proliferation not significantly different between treatment and control groups. Taken together, these data reinforce a necessary role for fibroblasts during tissue regeneration and show that beryllium nitrate inhibits normal fibroblast behavior.