506
A . A . M O S C O N A
mass, aggregates attain no characteristic organization (Berrill, 1945;
Grobstein and Zwilling, 1953; Grobstein, 1955b; Zwilling, 1959). The
size of this critical mass varies for different cell combinations and
environmental circumstances; probably, it represents marginal conditions for diffusion or retention of metabolites and nutrients, or provision
of essential cell products. Histogenesis in aggregates is also dependent on
relative concentrations of the different cell kinds (Moscona, 1956);
according to circumstances, the proportions of different cells essential
for normal differentiation of the aggregate may be similar to, or
different from those obtaining in the tissue of origin. For instance,
development of muscle in aggregates of 4-day chick limb-bud cells
occurs only if the concentration of myogenic cells is increased above
that in the intact limb bud (Moscona and Moscona, 1952); otherwise,
"dilution" by the chondrogenic cells prevents their histotypic expression. A transforming or inductive effect of chondroblasts on these early
myoblasts could be involved (Holtzer and Detwiler, 1953), resulting in
the development of practically the whole aggregate into a lump of
cartilage. However, the possibility that formation or retention of products of myoblastic cells or of metabolites essential for myogenesis might
be primarily involved cannot be excluded at present.
Development in aggregates depends on the state of differentiation of
their constituent cells at dissociation. According to available information, cells set upon a given course of development before dispersal
("determined" Waddington, 1940), tend to follow this course in
aggregates, while cells obtained before the onset of cytodetermination
may be more susceptible to the modifying effects of their environment
or of other cells (Grobstein, 1955b). Skin cells, dissociated from 5-day
chick-embryos, though structurally uniform, give rise in aggregates to
feather buds and other cutaneous differentiations (Weiss and James,
1955). Such structures are not found in aggregates containing ectodermal cells from considerably earlier embryos which, on the other
hand, give rise to diverse neural formations, as found by Zwilling (1959)
who also discussed the possibility of developmental interactions in
aggregates of such early embryonic cells. That in addition to the
retention of those features which were stabilized before dissociation
aggregating cells may also engage in inductive processes was clearly
demonstrated by Auerbach and Grobstein (1958); thus, in mixtures of
dissociated cells from embryonic-mouse metanephrogenic mesenchyme
and spinal cord, the latter-activated the former to form nephric tubules.
As suggested by Trinkaus (1956), it is not improbable that less readily
discernible inductive interactions between aggregating cells may play
a significant role in the histogenesis of aggregates particularly when
these are composed of cells from early embryos. Differentiation of
A . A . M O S C O N A
mass, aggregates attain no characteristic organization (Berrill, 1945;
Grobstein and Zwilling, 1953; Grobstein, 1955b; Zwilling, 1959). The
size of this critical mass varies for different cell combinations and
environmental circumstances; probably, it represents marginal conditions for diffusion or retention of metabolites and nutrients, or provision
of essential cell products. Histogenesis in aggregates is also dependent on
relative concentrations of the different cell kinds (Moscona, 1956);
according to circumstances, the proportions of different cells essential
for normal differentiation of the aggregate may be similar to, or
different from those obtaining in the tissue of origin. For instance,
development of muscle in aggregates of 4-day chick limb-bud cells
occurs only if the concentration of myogenic cells is increased above
that in the intact limb bud (Moscona and Moscona, 1952); otherwise,
"dilution" by the chondrogenic cells prevents their histotypic expression. A transforming or inductive effect of chondroblasts on these early
myoblasts could be involved (Holtzer and Detwiler, 1953), resulting in
the development of practically the whole aggregate into a lump of
cartilage. However, the possibility that formation or retention of products of myoblastic cells or of metabolites essential for myogenesis might
be primarily involved cannot be excluded at present.
Development in aggregates depends on the state of differentiation of
their constituent cells at dissociation. According to available information, cells set upon a given course of development before dispersal
("determined" Waddington, 1940), tend to follow this course in
aggregates, while cells obtained before the onset of cytodetermination
may be more susceptible to the modifying effects of their environment
or of other cells (Grobstein, 1955b). Skin cells, dissociated from 5-day
chick-embryos, though structurally uniform, give rise in aggregates to
feather buds and other cutaneous differentiations (Weiss and James,
1955). Such structures are not found in aggregates containing ectodermal cells from considerably earlier embryos which, on the other
hand, give rise to diverse neural formations, as found by Zwilling (1959)
who also discussed the possibility of developmental interactions in
aggregates of such early embryonic cells. That in addition to the
retention of those features which were stabilized before dissociation
aggregating cells may also engage in inductive processes was clearly
demonstrated by Auerbach and Grobstein (1958); thus, in mixtures of
dissociated cells from embryonic-mouse metanephrogenic mesenchyme
and spinal cord, the latter-activated the former to form nephric tubules.
As suggested by Trinkaus (1956), it is not improbable that less readily
discernible inductive interactions between aggregating cells may play
a significant role in the histogenesis of aggregates particularly when
these are composed of cells from early embryos. Differentiation of