LIMB REGENERATION IN SALAMANDERS 999 and X-rayed stumps covered with normal epidermis indicates that in the normal stumps nerve fibers grow into the epidermal wound epithelium covering the distal end of the stump.'**'* There the nerve endings make a synaptic junction with the epidermal cells.'’ In limbs witha normal nerve supply, this intimacy of nerves and epidermis isa prerequisite for regeneration, ” The nerves making this contact are afferent nerves, In the event that all afferent nerves are removed and the limb regenerates with an increased efferent supply,” the contact between nerves and epidermisisnot necessary for limb regeneration, ****! Presumably in this case contact between efferent nerves and other tissues performs the function necessary for limb regeneration, In X-rayed limbs after amputation, the nerves fail to enter the epidermis and regeneration fails, When the X-rayed limb stump has normal epidermis at its tip, nerves do enter the epidermis, and the internal changes necessary for regeneration occur, A reciprocal experiment has been performed, If the limb nerve still attached centrally is dissected from the limb, put to the side, and shielded during irradiation of the limb and then is replaced in the limb, such a nerve will make contact with the irradiated epidermis, and Iimb regeneration will occur,”? If either the epidermis or the nerve is not irradiated, it can make contact, and the trophic nerve function is performed, This trophic function apparently permits the flow of morphogenetic information between cells, Without that flow after denervationor X-irradiation, a limb does not begin to regenerate. Further research is necessary to Jetermine whether in other cases where trophic function has been decreased by irradiation it could be restored by normal grafts. cOPY ACKNOWLEDGMENTS BEST AVAILABLE This study is supported by grant G-23866 from the National Science Foundation and grant K3-HD-14,119 from the National Insti- tutes of Health, REFERENCES 1. V. V. Brunst, Some Problems of Regeneration, Quart. Rer. Biol., 36: 178- 206 (1961). 2. E. D. Hay, Regeneration, pp. 148, Holt, Rinehart & Winston, Inc., New York, 3. 1966, W. Luther, Zur Frage des Determinatlonszustandes von Kegerctrations- blastemen, Nalurwissenschaflen, 35: 30-31 (1948). 4. H. Ae L. Trampusch, The Action of X-rays on the Morphogenetic Field. II. Heterotoplo Skin on Irradiated Tails, Konink!, Ned. Akad. Welenschap Proc. Ser. C, 61: 530-545 (1958). 5, L. Lazard, Influence des greffes homologues et hétérologues sur Iu morphologie des régénérats de membres chez Amblysioma punctatum, Compt. Rend,, 249: 468-469 (1959).