14. C E L L A G G R E G A T E S
505
for a long time; whether these clusters incorporate a selected type of
cells, or cells in a certain phase of their functional cycle, is not known.
It is not unlikely that the changes in the adhesive properties of monolayer-cultured cells are due to alterations in cell-surface or extracellular
products in response to dispersal. Differences in the extracellular
mucopolysaccharides of cells grown in close contact and in dispersion
(Morris and Godman, 1960) might be indicative of such effects. O f
equally speculative but clearly suggestive relevance to this topic are two
lines of information which can be only mentioned here. First, there are
the changes in surface antigenicities of monolayer-grown cells (Weiler,
1959; Hogman, 1960); it might well be worth exploring whether or not
they are related to changes in cell-binding mechanisms. Second, there
is the increase in susceptibility to virus infection of cells grown in vitro
(Enders, Weiler and Robbins, 1949). Holland (1961) presented striking
evidence that the ability of normally non-infective cells to bind polio
virus increases rapidly in monolayer cultures in a manner indicative of
synthesis or unmasking of new receptor substances at the cell surface.
His findings indicate a highly suggestive correlation between decrease
in ability of dissociated, monolayer-grown cells to form coherent
fabrics, and increase in their virus-binding capacity. The possibility
seems worth entertaining that changes in synthesis or properties of
virus receptor-substances may be symptomatic of modifications occurring, perhaps concurrently, also in those products of the cell surface that
actually mediate cell attachment.
Decline in the ability of embryonic cells to aggregate when grown in
a dispersed state is accompanied by a reduction in their responsiveness
to inductive stimuli (Grobstein, 1962), by changes in histogenetic
properties (Moscona, 1960) and by alteration in biosynthesis of extracellular, matrix materials (Holtzer, Abbott, Lash and Holtzer, 1960).
Some of these points are discussed further on.
I I I .
T H E D E V E L O P M E N T OF A G G R E G A T E S
A. G E N E R A L
The most striking aspect of the aggregation of embryonic cells is the
ability of the reassociated cells to establish developmental relationships
and to construct tissues. Histotypic competence of aggregates depends
primarily on their cellular composition: aggregates consisting solely of
connective tissue or fibroblastic cells tend to become redispersed; pure
epithelial clusters show no identifiable tissue structure. Histogenesis is
also related to the size of the aggregate in that below a certain critical
505
for a long time; whether these clusters incorporate a selected type of
cells, or cells in a certain phase of their functional cycle, is not known.
It is not unlikely that the changes in the adhesive properties of monolayer-cultured cells are due to alterations in cell-surface or extracellular
products in response to dispersal. Differences in the extracellular
mucopolysaccharides of cells grown in close contact and in dispersion
(Morris and Godman, 1960) might be indicative of such effects. O f
equally speculative but clearly suggestive relevance to this topic are two
lines of information which can be only mentioned here. First, there are
the changes in surface antigenicities of monolayer-grown cells (Weiler,
1959; Hogman, 1960); it might well be worth exploring whether or not
they are related to changes in cell-binding mechanisms. Second, there
is the increase in susceptibility to virus infection of cells grown in vitro
(Enders, Weiler and Robbins, 1949). Holland (1961) presented striking
evidence that the ability of normally non-infective cells to bind polio
virus increases rapidly in monolayer cultures in a manner indicative of
synthesis or unmasking of new receptor substances at the cell surface.
His findings indicate a highly suggestive correlation between decrease
in ability of dissociated, monolayer-grown cells to form coherent
fabrics, and increase in their virus-binding capacity. The possibility
seems worth entertaining that changes in synthesis or properties of
virus receptor-substances may be symptomatic of modifications occurring, perhaps concurrently, also in those products of the cell surface that
actually mediate cell attachment.
Decline in the ability of embryonic cells to aggregate when grown in
a dispersed state is accompanied by a reduction in their responsiveness
to inductive stimuli (Grobstein, 1962), by changes in histogenetic
properties (Moscona, 1960) and by alteration in biosynthesis of extracellular, matrix materials (Holtzer, Abbott, Lash and Holtzer, 1960).
Some of these points are discussed further on.
I I I .
T H E D E V E L O P M E N T OF A G G R E G A T E S
A. G E N E R A L
The most striking aspect of the aggregation of embryonic cells is the
ability of the reassociated cells to establish developmental relationships
and to construct tissues. Histotypic competence of aggregates depends
primarily on their cellular composition: aggregates consisting solely of
connective tissue or fibroblastic cells tend to become redispersed; pure
epithelial clusters show no identifiable tissue structure. Histogenesis is
also related to the size of the aggregate in that below a certain critical