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merit, although when purposely placed in contact such aggregates
may fuse. One assumes that in 24 h the aggregates acquire a surface
layer of cells which are relatively non-adhesive at the side exposed to
the medium. Hence a cell population comprising many such cells
may be expected to yield an aggregation pattern consisting of numerous
small aggregates, and vice versa. This seems indeed to be the case.
Cells from dissociated whole limb-buds produce aggregates which,
perhaps because they are rapidly covered by epidermal cells, become
non-adhesive and remain quite small; liver cells, on the other hand,
cohere into large masses. At a more subtle level, such differences in
adhesiveness within the population of aggregating cells are involved
in other, less obvious pattern distinctions. It is of interest in this context
that the major features of these aggregation patterns are not narrowly
species-specific; homologous cells from chick- or mouse-embryos at
comparable stages of development aggregate under standard testing
conditions, into strikingly similar patterns (Moscona, 1962c).
As mentioned above, aggregation is markedly affected by the
developmental stage of the cells, i.e. their state of differentiation when
dissociated. Under standard conditions of testing by rotation, cells
from the same tissue but from progressively older embryos show a
gradual decline in their ability to aggregate, in that smaller aggregates
are formed and more cells remain free. Cells dissociated from late
foetal and adult tissues usually do not form compact aggregates
although under suitable conditions they can be propagated in culture.
These findings, originally described for embryonic chick retina (Figs.
4-9) and liver cells (Moscona and Weis, 1961; Moscona, 1961c), were
recently extended to lung cells in hanging drops (Grover, 1962). The
phenomenon of age-dependent decline in adhesiveness of dissociated
cells recalls a similar decline occurring normally in the development and
maturation of thymus, lymph nodes, bone marrow, in vivo and in vitro
(Auerbach, 1961) as well as in other tissues undergoing morphogenetic
dissociation.
While the precise causes of these age-dependent changes in the
ability of dissociated cells to aggregate are far from established, their
correlation with increasing specialization of the cells with progressive
development is suggestive. Non-reattachment of cells could be due to
"permanent" injury at dissociation; since the cells are able to proliferate individually in culture, and since equally treated cells from
younger embryos are not thus altered, this possibility seems, at present,
unlikely. It seems more likely that the effect might be related to
specialization accompanying restrictions and channeling of metabolic
functions in differentiated cells. As suggested above, histotypic recohesion may depend on the ability of cells to form specific products at
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