VII.
LIMB
MORPHOGENESIS
317
as in polydactylous controls. I have already cited the results of similar
experiments between genetically wingless mesoderm and normal ectoderm which indicated that the mutant mesoderm was deficient in
something required for the maintenance of the ridge.
All of the above evidence indicated to us that there is some factor in
the limb-bud mesoderm upon which the persistence of the ectodermal
ridge in a thickened and inductively active condition depended. Furthermore the evidence points to an asymmetrical distribution of the mesodermal factor and places upon it a key role in the patterning of a limb.
Since outgrowth of the limb is associated with thickened ridge (or some
property which results from this) and since the persistence of ridge
thickening is in conformity with the pattern of distribution of this
hypothetical mesodermal factor, variations in the latter can be responsible for deviations from the normal (Zwilling, 1956e). Amelia (absence
of limbs) may be due to the absence of the maintenance factor, ectromelia (loss of some distal elements) may result from deficiencies, while
Polydactyly and other conditions characterized by the development of
accessory limb structures may be due to both an excessive amount and
an abnormally extensive distribution of the factor.
Saunders, Gasseling and Gfeller, 1958; Saunders, Gasseling and
Bertizal, 1959; and Amprino and Camosso, 1958a, b; 1959 have independently performed and almost simultaneously reported the same
experiment. When an entire limb bud is grafted to a foreign site or
placed in an inverted position on the normal site a normal single limb,
with altered orientation in the latter case, is formed. When the distal
tip of a limb bud is grafted to a non-limb site or replaced on a proximal
limb stump in such a way that the two an tero-posterior axes conform,
distal parts for a normal single limb develop. However, when the distal
tip is rotated through 180° and then replaced on the proximal stump in
such a way that the original anterior end of the tip is in contact with the
posterior end of the stump (i.e. the distal tip is inverted) more than
70% of the limbs develop a supernumerary manus in addition to the
normal one. In a few cases three sets of digits may form. When two
duplicate sets of digits formed they were mirror-images of each other.
The marked resemblance of these cases of duplication which resulted
from a surgical procedure to the genetic duplicate condition (Warren,
1944; Landauer, 1956) is striking. Both sets of authors present evidence
that the accessory structures form from the tissue of the inverted tip.
Amprino and Camosso interpret these experiments to indicate that
'. . ., their development apparently depends on influences exerted by
the proximal portion of the wing bud . . .'. These 'influences' are visualized to emanate from the more 'determined' or differentiated proximal
tissues and effect the less 'determined' distal tissues so that they form
LIMB
MORPHOGENESIS
317
as in polydactylous controls. I have already cited the results of similar
experiments between genetically wingless mesoderm and normal ectoderm which indicated that the mutant mesoderm was deficient in
something required for the maintenance of the ridge.
All of the above evidence indicated to us that there is some factor in
the limb-bud mesoderm upon which the persistence of the ectodermal
ridge in a thickened and inductively active condition depended. Furthermore the evidence points to an asymmetrical distribution of the mesodermal factor and places upon it a key role in the patterning of a limb.
Since outgrowth of the limb is associated with thickened ridge (or some
property which results from this) and since the persistence of ridge
thickening is in conformity with the pattern of distribution of this
hypothetical mesodermal factor, variations in the latter can be responsible for deviations from the normal (Zwilling, 1956e). Amelia (absence
of limbs) may be due to the absence of the maintenance factor, ectromelia (loss of some distal elements) may result from deficiencies, while
Polydactyly and other conditions characterized by the development of
accessory limb structures may be due to both an excessive amount and
an abnormally extensive distribution of the factor.
Saunders, Gasseling and Gfeller, 1958; Saunders, Gasseling and
Bertizal, 1959; and Amprino and Camosso, 1958a, b; 1959 have independently performed and almost simultaneously reported the same
experiment. When an entire limb bud is grafted to a foreign site or
placed in an inverted position on the normal site a normal single limb,
with altered orientation in the latter case, is formed. When the distal
tip of a limb bud is grafted to a non-limb site or replaced on a proximal
limb stump in such a way that the two an tero-posterior axes conform,
distal parts for a normal single limb develop. However, when the distal
tip is rotated through 180° and then replaced on the proximal stump in
such a way that the original anterior end of the tip is in contact with the
posterior end of the stump (i.e. the distal tip is inverted) more than
70% of the limbs develop a supernumerary manus in addition to the
normal one. In a few cases three sets of digits may form. When two
duplicate sets of digits formed they were mirror-images of each other.
The marked resemblance of these cases of duplication which resulted
from a surgical procedure to the genetic duplicate condition (Warren,
1944; Landauer, 1956) is striking. Both sets of authors present evidence
that the accessory structures form from the tissue of the inverted tip.
Amprino and Camosso interpret these experiments to indicate that
'. . ., their development apparently depends on influences exerted by
the proximal portion of the wing bud . . .'. These 'influences' are visualized to emanate from the more 'determined' or differentiated proximal
tissues and effect the less 'determined' distal tissues so that they form