DIFFERENTIATION OF KIDNEY MESENCHYME
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"critical mass" or "critical density" of embryonic cells capable of differentiating and that further fragmentation of this mass prevents morphogenesis (Grobstein and Zwilling, 1953; Grobstein, 1955b). The priming
stimulus in tubule induction may, in fact, be merely a trigger that alters
the surface characteristics of the responding cells in such a way as to
bring them into close contact, the resultant aggregates representing units
of such "critical mass."
Grobstein (1966) points out that, in the formation of kidney tubules,
such morphogenetic events leading to pretubular aggregates (also called
"condensates" below) seem to precede the first detectable differentiative
changes within the cells. The role of such homotypic interactions, the
formation of pretubular cell clusters and their temporal (as well as
causal) relationships to cytodifferentiation will be discussed below.
Finally, the molecular basis of such exogenous control systems deserves
some comments.
Today, we may agree that morphogenesis is an actual reflection of
chemodifferentiation, representing changes in the production of macromolecular compounds controlled by the cellular genome. Hence it is of
major importance to see whether an inductive process involves activation of the genetic material or changes in the transference of this information to the machinery concerned with protein synthesis. An inductor,
therefore, probably (at some stage) interferes with the genome or its
transcription system, although not much is known of these control
mechanisms in metazoan cells.
B. The Experimental Setup
The experimental procedure is based on the original findings and
methods of Grobstein (1955a), described above.
In the studies reported below, a setup was used where mesenchymal
tissue isolated from 11- to 12-day-old embryonic mouse kidney rudiments
was cultured in a petri dish on a Millipore filter under which the inducing
tissue was cemented with agar. The culture technique is described in
detail in Fig. 1. Mesenchymes cultured alone on the Millipore filter or
in transfilter contact with adult mouse liver tissue do not form aggregates
and tubules and thus have served as controls in various experiments.
The transfilter method used in our studies has the great advantage of
providing an easy way of controlling the duration of the inductive
stimulus. The inductor can easily be removed without any harmful effects
on the responding tissue. Also, the responding material can easily be
collected for analysis without contamination by cells from the inductor
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