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CHARLES S. THORNTON
regeneration when administered at the blastema] stages (Hay, 1956).
Perhaps prolactin, like GH (Wilkerson, 1963), is also most effective
at the blastemal proliferation stage so that its inhibition by thyroxine
would influence most critically the growth phase of regeneration. Since
we do not have enough information on the interaction of thyroxine and
prolactin in urodeles, these thoughts are entirely speculative. Nevertheless, it is interesting to learn that exogenous prolactin induces the "water
drive" in the red eft (the "second metamorphosis," Grant, 1961), whereas
exogenous thyroxine induces a "land drive" in adult (aquatic) newts
(Grant and Cooper, 1965). There is a suggestion here, therefore, of a
possible prolactin-thyroxine antagonism in newts—a possibility which
invites further analysis.
V. Discussion and Conclusions
From the foregoing account of limb regeneration, although brief and
selective by requirements of space, one overriding problem emerges,
"How can we account for the morphogenesis of the blastema?" It has
become clear, in recent years, that the cells which make up the blastema
are derived from the various tissues of the remaining limb stump. It is
becoming increasingly clearer, also, that the "dedifferentiated" blastemal
cells apparently retain their tissue specificity even though morphological
identity is lost (or at least seems to be so with our present methods of
analysis). The limited metaplasia represented by transformation of
connective tissue cells to cartilage is not unique to regenerating limbs
and has long been known in pathology. We are left, therefore, with an
aggregation of morphologically similar, but genetically tissue-specific,
mesenchymatous cells which undoubtedly become intermingled and
scrambled as they proliferate in the blastema. How do these cells reassort
themselves during differentiation to undergo histogenesis? The mechanisms are equally unknown as investigated in embryonic systems by
Moscona and others, but the problems are similar to those of regeneration. The presence of stump tissues, an apparent fountainhead of morphogenetic control, is yet of little help in understanding the mechanisms
involved since blastemata isolated from stump influences, even in very
young stages, can nevertheless undergo organogenesis and histogenesis.
A consistent and impressive phenomenon in blastemal morphogenesis
is that only those structures are formed which are distal to those present
at the amputation level of the stump. Wherever the level of amputation
along the limb may be, it is the missing parts and only the missing parts
which are reconstituted. Yet this rule is not as simple and direct as it
CHARLES S. THORNTON
regeneration when administered at the blastema] stages (Hay, 1956).
Perhaps prolactin, like GH (Wilkerson, 1963), is also most effective
at the blastemal proliferation stage so that its inhibition by thyroxine
would influence most critically the growth phase of regeneration. Since
we do not have enough information on the interaction of thyroxine and
prolactin in urodeles, these thoughts are entirely speculative. Nevertheless, it is interesting to learn that exogenous prolactin induces the "water
drive" in the red eft (the "second metamorphosis," Grant, 1961), whereas
exogenous thyroxine induces a "land drive" in adult (aquatic) newts
(Grant and Cooper, 1965). There is a suggestion here, therefore, of a
possible prolactin-thyroxine antagonism in newts—a possibility which
invites further analysis.
V. Discussion and Conclusions
From the foregoing account of limb regeneration, although brief and
selective by requirements of space, one overriding problem emerges,
"How can we account for the morphogenesis of the blastema?" It has
become clear, in recent years, that the cells which make up the blastema
are derived from the various tissues of the remaining limb stump. It is
becoming increasingly clearer, also, that the "dedifferentiated" blastemal
cells apparently retain their tissue specificity even though morphological
identity is lost (or at least seems to be so with our present methods of
analysis). The limited metaplasia represented by transformation of
connective tissue cells to cartilage is not unique to regenerating limbs
and has long been known in pathology. We are left, therefore, with an
aggregation of morphologically similar, but genetically tissue-specific,
mesenchymatous cells which undoubtedly become intermingled and
scrambled as they proliferate in the blastema. How do these cells reassort
themselves during differentiation to undergo histogenesis? The mechanisms are equally unknown as investigated in embryonic systems by
Moscona and others, but the problems are similar to those of regeneration. The presence of stump tissues, an apparent fountainhead of morphogenetic control, is yet of little help in understanding the mechanisms
involved since blastemata isolated from stump influences, even in very
young stages, can nevertheless undergo organogenesis and histogenesis.
A consistent and impressive phenomenon in blastemal morphogenesis
is that only those structures are formed which are distal to those present
at the amputation level of the stump. Wherever the level of amputation
along the limb may be, it is the missing parts and only the missing parts
which are reconstituted. Yet this rule is not as simple and direct as it