320
EDGAR
ZWILLING
have been led to a similar viewpoint. In their experiments two types of
operation were performed: one in which the entire wing bud was excised
and in its place was grafted an ectoderm-free limb-bud mesoblast and
the other in which the ectodermal ridge was kept and tacked to the
distal edge of the grafted ectoderm-free mesoblast. This operation left
the graft free of ectoderm except along the distal margin. In the absence
of the ridge most of the mesoblast degenerated within 24 hours of the
operation. When a ridge was on the distal surface, vascularization in
association with it (including collateral blood vessels) was quickly
established and the mesoblast, though bare on most of both lateral
surfaces, was healthy and developed normally. Such evidence leaves
little doubt that the ectodermal ridge exerts some influence on the
development of marginal vascularization, but what role these blood
vessels may play in promoting limb outgrowth is not clear.
Bell et al. (1959a) have called attention to the possible importance of
the basement membrane in limb development. They suggest that this
structure may, possibly, interfere with limb outgrowth of mesoblasts
which lack an ectodermal covering and that outgrowth occurs only after
the membrane has been removed or after it breaks down. The implication left is that a normal basement membrane is active as long as it is in
contact with its own ectoderm and mesoderm while one that is deprived
of its ectoderm may become 'static' and 'constraining' to outgrowth. It
is intriguing to consider the basement membrane as an important
contributor to limb development largely because of its origin. As Bell
points out, this structure has a dual origin (Weiss and Ferris, 1954;
Edds, 1958), with both epithelium and connective tissue making important contributions (this may be translated to ectoderm and mesoderm for the limb buds). Since I feel that the majority of current
evidence still indicates that some sort of reciprocal relation between
limb ectoderm and mesoderm is important for the elaboration of an
appendage then a structure which has the dual origin of the basement
membrane becomes a likely candidate for the site of this interaction.
However, I tend to favour a more positive view than that suggested by
Bell. It is conceivable that an intact basement membrane may promote
cell migration along its inner surface and that such migration may be
an important, possibly essential, feature of the laying down of the
presumptive distal limb structures. In the absence of ectoderm, cell
movements sufficient to establish limb element anlagen may continue
as long as the basement membrane is intact. When the membrane
breaks down such activity probably stops. The fact that limb outgrowth
(in the chick) does not occur when the mesoblast is covered with nonlimb ectoderm (Zwilling, 1955) indicates some degree of specificity for
the ectodermal contribution to the basement membrane. Experiments
EDGAR
ZWILLING
have been led to a similar viewpoint. In their experiments two types of
operation were performed: one in which the entire wing bud was excised
and in its place was grafted an ectoderm-free limb-bud mesoblast and
the other in which the ectodermal ridge was kept and tacked to the
distal edge of the grafted ectoderm-free mesoblast. This operation left
the graft free of ectoderm except along the distal margin. In the absence
of the ridge most of the mesoblast degenerated within 24 hours of the
operation. When a ridge was on the distal surface, vascularization in
association with it (including collateral blood vessels) was quickly
established and the mesoblast, though bare on most of both lateral
surfaces, was healthy and developed normally. Such evidence leaves
little doubt that the ectodermal ridge exerts some influence on the
development of marginal vascularization, but what role these blood
vessels may play in promoting limb outgrowth is not clear.
Bell et al. (1959a) have called attention to the possible importance of
the basement membrane in limb development. They suggest that this
structure may, possibly, interfere with limb outgrowth of mesoblasts
which lack an ectodermal covering and that outgrowth occurs only after
the membrane has been removed or after it breaks down. The implication left is that a normal basement membrane is active as long as it is in
contact with its own ectoderm and mesoderm while one that is deprived
of its ectoderm may become 'static' and 'constraining' to outgrowth. It
is intriguing to consider the basement membrane as an important
contributor to limb development largely because of its origin. As Bell
points out, this structure has a dual origin (Weiss and Ferris, 1954;
Edds, 1958), with both epithelium and connective tissue making important contributions (this may be translated to ectoderm and mesoderm for the limb buds). Since I feel that the majority of current
evidence still indicates that some sort of reciprocal relation between
limb ectoderm and mesoderm is important for the elaboration of an
appendage then a structure which has the dual origin of the basement
membrane becomes a likely candidate for the site of this interaction.
However, I tend to favour a more positive view than that suggested by
Bell. It is conceivable that an intact basement membrane may promote
cell migration along its inner surface and that such migration may be
an important, possibly essential, feature of the laying down of the
presumptive distal limb structures. In the absence of ectoderm, cell
movements sufficient to establish limb element anlagen may continue
as long as the basement membrane is intact. When the membrane
breaks down such activity probably stops. The fact that limb outgrowth
(in the chick) does not occur when the mesoblast is covered with nonlimb ectoderm (Zwilling, 1955) indicates some degree of specificity for
the ectodermal contribution to the basement membrane. Experiments