284
LAURI SAXEN ET AL.
culture, when the explant consists of numerous tubules, the intervening
cells may well be too sparse to encounter other like cells in sufficient
quantities to form aggregates.
B. Cell Division
The relation of differentiation to DNA synthesis and mitosis is an old
enigma, which ought to be discussed in connection with kidney tubule
differentiation. It has been postulated in several contexts that cells involved in DNA synthesis and mitosis do not differentiate and that they
have to undergo a critical or terminal mitosis before they can express
their specialized character, for instance by the synthesis of a special
protein (see Holtzer, 1961; Wessells, 1964a). There are instances where
cell division seems to be a prerequisite for subsequent differentiation
characterized by specific synthetic ability. Thus it has been shown that
the acinar cells of the mammary gland have to go through mitosis before
they are able to synthesize specific protein (Stockdale and Topper, 1966;
Lockwood et al., 1967). Antibody production may also be considered an
example of cell differentiation. It is known that during the secondary
immune response the lymphoid cells have to undergo mitosis before they
can synthesize antibodies in large quantities (Dutton et al., 1960; Makela
and Nossal, 1962). It might even be thought that one of the main tasks
of the inductor would be to promote the "critical" cell division needed for
cell specialization.
Mitotic figures are frequent in the loose metanephrogenic mesenchyme
before any cell condensation is discernible. They are also seen occasionally in the condensates and are numerous when the tubules start growing.
At the time of formation of the first condensates, a large proportion of the
cells synthesize DNA, as revealed in radioautography with tritiumlabeled thymidine, and labeled cells are seen in the condensates as well.
When the tubules mature, their cells pick up more label than the surrounding loose mesenchymal cells (Rapola et al., 1963). The total uptake
of tritiated thymidine into acid-insoluble form by the explants decreases
during the first 10 hours of cultivation, but thereafter increases sharply.
A similar, although less marked, rise has been noted in the noninduced
explants as well (Fig. 2).
Sobel (1966) has extended studies of the relationship of cell division
to tubule differentiation in vitro. He has shown that mitoses and active
DNA synthesis take place in the early condensates. He could also show
that inhibition of DNA synthesis by 5-fluorodeoxyuridine in the early
condensates prevents subsequent tubule differentiation. These results are
LAURI SAXEN ET AL.
culture, when the explant consists of numerous tubules, the intervening
cells may well be too sparse to encounter other like cells in sufficient
quantities to form aggregates.
B. Cell Division
The relation of differentiation to DNA synthesis and mitosis is an old
enigma, which ought to be discussed in connection with kidney tubule
differentiation. It has been postulated in several contexts that cells involved in DNA synthesis and mitosis do not differentiate and that they
have to undergo a critical or terminal mitosis before they can express
their specialized character, for instance by the synthesis of a special
protein (see Holtzer, 1961; Wessells, 1964a). There are instances where
cell division seems to be a prerequisite for subsequent differentiation
characterized by specific synthetic ability. Thus it has been shown that
the acinar cells of the mammary gland have to go through mitosis before
they are able to synthesize specific protein (Stockdale and Topper, 1966;
Lockwood et al., 1967). Antibody production may also be considered an
example of cell differentiation. It is known that during the secondary
immune response the lymphoid cells have to undergo mitosis before they
can synthesize antibodies in large quantities (Dutton et al., 1960; Makela
and Nossal, 1962). It might even be thought that one of the main tasks
of the inductor would be to promote the "critical" cell division needed for
cell specialization.
Mitotic figures are frequent in the loose metanephrogenic mesenchyme
before any cell condensation is discernible. They are also seen occasionally in the condensates and are numerous when the tubules start growing.
At the time of formation of the first condensates, a large proportion of the
cells synthesize DNA, as revealed in radioautography with tritiumlabeled thymidine, and labeled cells are seen in the condensates as well.
When the tubules mature, their cells pick up more label than the surrounding loose mesenchymal cells (Rapola et al., 1963). The total uptake
of tritiated thymidine into acid-insoluble form by the explants decreases
during the first 10 hours of cultivation, but thereafter increases sharply.
A similar, although less marked, rise has been noted in the noninduced
explants as well (Fig. 2).
Sobel (1966) has extended studies of the relationship of cell division
to tubule differentiation in vitro. He has shown that mitoses and active
DNA synthesis take place in the early condensates. He could also show
that inhibition of DNA synthesis by 5-fluorodeoxyuridine in the early
condensates prevents subsequent tubule differentiation. These results are