236
CHARLES S. THORNTON
limbs grafted orthotopically to normal larvae. The implanted limbs were
maintained in aneurogenic, or sparsely innervated, condition by repeated
section of host brachial nerves, yet supernumerary limbs developed on
these limbs with the same frequency (30%) as in those aneurogenic limb
grafts that were allowed to become innervated (28.5% frequency). Thus,
accessory limb induction in these aneurogenic limbs was not at all correlated with nerve ingrowth. It is particularly interesting that we have
been unable to induce regeneration of denervated limb stumps by means
of severe mechanical trauma alone (see also Singer et al., 1957); after
denervation, supernumeraries and regenerates occurred only after transplantation of the limb! Thus transplantation would seem to constitute a
particularly important factor for the synthesis of trophic substance by
nonneural tissues. How transplantation differs from other forms of tissue
trauma is not yet known, but, hopefully, further study of this difference
may provide a clue to an understanding of the trophic influence in limb
regeneration.
IV. The Influence of Hormones on Limb Regeneration
Interest in the influence of endocrine glands on regeneration began
with the pioneering works of Walter (1910), studying effects of thyroidectomy, and of Schotte (1926), who described effects of hypophysectomy. Both investigators used the European newt, Triton, and discovered that limb regeneration was dependent on the normal activities of
these two glands. More recently, Richardson (1945) has reported that
the American newt, Notophthalmus,
fails to regenerate limbs when amputation is performed after, or concomitantly with, hypophysectomy.
However, when hypophysectomy is delayed for 3 or more days after
amputation, some limbs regenerate, although atypically (Schotte and
Hall, 1952). The number of positive cases of regeneration increases as
the interval between amputation and hypophysectomy is increased. Thus,
when amputation precedes hypophysectomy by 3 to 10 days, only 12%
of limbs failed to regenerate, although over half the positive cases were
abortive or delayed. When amputation preceded hypophysectomy by 13
days or more, there were still some cases of abortive regeneration but no
cases of regenerative failure (see also Inoue, 1956). These results were
interpreted by Schotte and Hall (1952) to demonstrate that the action of
the pituitary was required solely for the wound healing and dedifferentiation phases of limb regeneration but not for the phases of growth and
differentiation.
Replacement therapy proved to be m effective means of alleviating the
CHARLES S. THORNTON
limbs grafted orthotopically to normal larvae. The implanted limbs were
maintained in aneurogenic, or sparsely innervated, condition by repeated
section of host brachial nerves, yet supernumerary limbs developed on
these limbs with the same frequency (30%) as in those aneurogenic limb
grafts that were allowed to become innervated (28.5% frequency). Thus,
accessory limb induction in these aneurogenic limbs was not at all correlated with nerve ingrowth. It is particularly interesting that we have
been unable to induce regeneration of denervated limb stumps by means
of severe mechanical trauma alone (see also Singer et al., 1957); after
denervation, supernumeraries and regenerates occurred only after transplantation of the limb! Thus transplantation would seem to constitute a
particularly important factor for the synthesis of trophic substance by
nonneural tissues. How transplantation differs from other forms of tissue
trauma is not yet known, but, hopefully, further study of this difference
may provide a clue to an understanding of the trophic influence in limb
regeneration.
IV. The Influence of Hormones on Limb Regeneration
Interest in the influence of endocrine glands on regeneration began
with the pioneering works of Walter (1910), studying effects of thyroidectomy, and of Schotte (1926), who described effects of hypophysectomy. Both investigators used the European newt, Triton, and discovered that limb regeneration was dependent on the normal activities of
these two glands. More recently, Richardson (1945) has reported that
the American newt, Notophthalmus,
fails to regenerate limbs when amputation is performed after, or concomitantly with, hypophysectomy.
However, when hypophysectomy is delayed for 3 or more days after
amputation, some limbs regenerate, although atypically (Schotte and
Hall, 1952). The number of positive cases of regeneration increases as
the interval between amputation and hypophysectomy is increased. Thus,
when amputation precedes hypophysectomy by 3 to 10 days, only 12%
of limbs failed to regenerate, although over half the positive cases were
abortive or delayed. When amputation preceded hypophysectomy by 13
days or more, there were still some cases of abortive regeneration but no
cases of regenerative failure (see also Inoue, 1956). These results were
interpreted by Schotte and Hall (1952) to demonstrate that the action of
the pituitary was required solely for the wound healing and dedifferentiation phases of limb regeneration but not for the phases of growth and
differentiation.
Replacement therapy proved to be m effective means of alleviating the