254
LAURI SAXEN ET AL.
merits with inductor tissues labeled with tritiated leucine demonstrated
transmission of labeled materials through the filter, and this passage
showed certain correspondences to the transmission of the inductive
effect under various experimental conditions (interposition of cellophane,
reduction of the mass of the inductor tissue, increase of the distance
between the interactants, etc.) (Koch and Grobstein, 1963). Despite these
suggestive results, no "inductor substance" has yet been isolated for
induction of kidney tubules (or any other interactive system), and both
killed tissues and tissue fractions have proved ineffective when tested for
their inductive capacity on metanephric blastema.
Another point of great interest is the kinetics of the induction process
and the stabilization of determination. In several interactive systems,
including tubule induction, a minimum time has proved necessary for
the establishment of induction. A transfilter setup provides good possibilities for such studies, and Grobstein (1961, 1963) has shown that
transfilter contact for as long as 20 to 30 hours is required for subsequent
independent differentiation of the mesenchyme. Whether this is due to a
"traveling" of the hypothetical inductor substance in the filter membrane
or to some other mechanism cannot be decided, but recent results in our
laboratory suggest that this may be the case. Miettinen (unpublished)
has performed experiments in which transfilter cultures of the usual type
(see page 256) were set up, and after 24 hours the mesenchyme was replaced with a second set of metanephrogenic blastemas. By virtue of this
"precultivation" of the inductor-filter system, the minimum time of
induction for the second mesenchyme could be reduced to about 8 hours,
suggesting that something might have been stored in the filter during the
first stage of the experiment. Another approach to the problem of the
stabilization of induction will be considered later in this review—where
induction was prevented by actinomycin D after different time intervals
(Jainchill et al, 1964; Koskimies, 1967b).
Not much is known of the mechanism of this (or any other) inductive
interaction in higher animals. As Grobstein (1963) has pointed out, however, the very diversity of the products of this morphogenetic interaction
indicates that we can hardly be dealing with a single-step process, but
rather with a chain of differentiative interactions, as shown in the determination of amphibian CNS by Saxen et al (1964). The first step is
evidently a heterotypic interaction (between the ureteric bud and
metanephrogenic mesenchyme), but this may be followed by homotypic
interactive processes between like cells in the responding tissue (Grobstein, 1962). Several earlier experiments have shown that there is a
LAURI SAXEN ET AL.
merits with inductor tissues labeled with tritiated leucine demonstrated
transmission of labeled materials through the filter, and this passage
showed certain correspondences to the transmission of the inductive
effect under various experimental conditions (interposition of cellophane,
reduction of the mass of the inductor tissue, increase of the distance
between the interactants, etc.) (Koch and Grobstein, 1963). Despite these
suggestive results, no "inductor substance" has yet been isolated for
induction of kidney tubules (or any other interactive system), and both
killed tissues and tissue fractions have proved ineffective when tested for
their inductive capacity on metanephric blastema.
Another point of great interest is the kinetics of the induction process
and the stabilization of determination. In several interactive systems,
including tubule induction, a minimum time has proved necessary for
the establishment of induction. A transfilter setup provides good possibilities for such studies, and Grobstein (1961, 1963) has shown that
transfilter contact for as long as 20 to 30 hours is required for subsequent
independent differentiation of the mesenchyme. Whether this is due to a
"traveling" of the hypothetical inductor substance in the filter membrane
or to some other mechanism cannot be decided, but recent results in our
laboratory suggest that this may be the case. Miettinen (unpublished)
has performed experiments in which transfilter cultures of the usual type
(see page 256) were set up, and after 24 hours the mesenchyme was replaced with a second set of metanephrogenic blastemas. By virtue of this
"precultivation" of the inductor-filter system, the minimum time of
induction for the second mesenchyme could be reduced to about 8 hours,
suggesting that something might have been stored in the filter during the
first stage of the experiment. Another approach to the problem of the
stabilization of induction will be considered later in this review—where
induction was prevented by actinomycin D after different time intervals
(Jainchill et al, 1964; Koskimies, 1967b).
Not much is known of the mechanism of this (or any other) inductive
interaction in higher animals. As Grobstein (1963) has pointed out, however, the very diversity of the products of this morphogenetic interaction
indicates that we can hardly be dealing with a single-step process, but
rather with a chain of differentiative interactions, as shown in the determination of amphibian CNS by Saxen et al (1964). The first step is
evidently a heterotypic interaction (between the ureteric bud and
metanephrogenic mesenchyme), but this may be followed by homotypic
interactive processes between like cells in the responding tissue (Grobstein, 1962). Several earlier experiments have shown that there is a