VII.
LIMB MORPHOGENESIS
305
represented 'self-differentiating' systems with strong 'mosaic' properties.
The development of flank and intracoelomic grafting techniques by
Hamburger (1938, 1939) enabled him to do some of the first precise
experiments with an amniote limb system. Hamburger was able to
demonstrate that axial relations were already stabilized ('determined')
in even the earliest limb buds (of Stage 17, Hamburger and Hamilton,
1951), and was able to follow patterns of innervation of limbs in a
foreign site as well as the development of limbs lacking innervation.
In many respects Hamburger's contributions represent the foundations
for most of the modern studies of limb development.
In sharp contrast with the earlier phase of experimental analysis of
limb development, most of the more recent studies have begun with a
limb bud, more or less advanced. Most of the material presented in the
following pages is concerned with studies carried out during the past
15-20 years.
II. An Hypothesis of Limb Development
Recent advances in the study of limb morphogenesis have brought us
close to the point where we may have some basis for embarking on
approaches designed to elucidate the molecular factors involved in the
elaboration of limbs. While all of the investigators who are active in
these studies do not agree with it, I should like, as a point of departure
for this discussion, to present an hypothesis of limb development which
has the merit of unifying most of the known facts. This hypothesis
has been elaborated, largely by myself (Zwilling, 1956e) and Saunders
(Saunders, Cairns and Gasseling, 1957) and is based on our experimental
observations, which are supported by those of others. I shall expand on
the evidence for this hypothesis later, but its major features are as
follows:
(1) There is (see below) a dearth of knowledge about the processes
which lead to the initiation of limb development. The best information
indicates that it is the presumptive limb mesoderm which is first activated.
(2) Shortly after it is stabilized in the direction of limb development
the mesoderm influences the overlying ectoderm and a system of
reciprocal dependence between the two components is established. The
chief morphological indication that the ectoderm has acquired an active
role in limb formation is the appearance, in amniote embryos as well as
some of the anamniotes, of the apical ectodermal ridge (Epidermis-leiste,
calotte épidermique). In many amphibia there is a thickened distal ectodermal cap instead of a ridge.
(3) In this interacting system the mesoderm continues a sequential
LIMB MORPHOGENESIS
305
represented 'self-differentiating' systems with strong 'mosaic' properties.
The development of flank and intracoelomic grafting techniques by
Hamburger (1938, 1939) enabled him to do some of the first precise
experiments with an amniote limb system. Hamburger was able to
demonstrate that axial relations were already stabilized ('determined')
in even the earliest limb buds (of Stage 17, Hamburger and Hamilton,
1951), and was able to follow patterns of innervation of limbs in a
foreign site as well as the development of limbs lacking innervation.
In many respects Hamburger's contributions represent the foundations
for most of the modern studies of limb development.
In sharp contrast with the earlier phase of experimental analysis of
limb development, most of the more recent studies have begun with a
limb bud, more or less advanced. Most of the material presented in the
following pages is concerned with studies carried out during the past
15-20 years.
II. An Hypothesis of Limb Development
Recent advances in the study of limb morphogenesis have brought us
close to the point where we may have some basis for embarking on
approaches designed to elucidate the molecular factors involved in the
elaboration of limbs. While all of the investigators who are active in
these studies do not agree with it, I should like, as a point of departure
for this discussion, to present an hypothesis of limb development which
has the merit of unifying most of the known facts. This hypothesis
has been elaborated, largely by myself (Zwilling, 1956e) and Saunders
(Saunders, Cairns and Gasseling, 1957) and is based on our experimental
observations, which are supported by those of others. I shall expand on
the evidence for this hypothesis later, but its major features are as
follows:
(1) There is (see below) a dearth of knowledge about the processes
which lead to the initiation of limb development. The best information
indicates that it is the presumptive limb mesoderm which is first activated.
(2) Shortly after it is stabilized in the direction of limb development
the mesoderm influences the overlying ectoderm and a system of
reciprocal dependence between the two components is established. The
chief morphological indication that the ectoderm has acquired an active
role in limb formation is the appearance, in amniote embryos as well as
some of the anamniotes, of the apical ectodermal ridge (Epidermis-leiste,
calotte épidermique). In many amphibia there is a thickened distal ectodermal cap instead of a ridge.
(3) In this interacting system the mesoderm continues a sequential