DIFFERENTIATION OF KIDNEY MESENCHYME
253
of kidney tubules in the metanephrogenic mesenchyme. Our intention is
to summarize the main features of the induction of this differentiative
process and to review some of the subsequent events analyzed in our
laboratory.
A. Tissue Interaction in the Development of the Kidney Tubules
Early experimental work on kidney morphogenesis had suggested an
inductive effect exerted by the epithelial bud of the Wolffian duct. The
destruction of this led to failure of the metanephric blastema to differentiate into kidney tubules (Gruenwald, 1937, 1942, 1952). Clifford
Grobstein succeeded in separating these two intimately associated components, the epithelial bud and the metanephrogenic mesenchymal
blastema, in mouse embryos. During subsequent cultivation in vitro the
isolated metanephric blastema failed to differentiate, and so did the
epithelial ureteric bud when cultured alone. When these two tissue components were experimentally combined and grown together as an organ
culture, tubule formation was triggered in the metanephric blastema
(Grobstein, 1953, 1955a, 1959). The ureteric bud was not the only
structure able to induce tubule formation in the metanephrogenic blastema, but some other embryonic tissues seemed to possess a similar
stimulating capacity, like the "heterogenous" inductors known from
amphibian embryology. The most potent of these was the dorsal half of
the embryonic spinal cord, which has subsequently been employed in a
variety of experiments as an easily available and potent inductor. This
relatively unspecific nature of induction should always be borne in mind,
and even heterologous tissues (chick spinal cord) have been found to act
as inductors of tubule formation in mouse nephric blastema (Grobstein,
1955a).
The morphogenetic interaction between the mesenchyme and its
inductor does not require cell-to-cell contact between the interactants.
These can be separated by porous membrane filters, and Grobstein showed
in 1957 that the inductive effect can be transmitted over a distance of
20 to 30 [x and through pores of approximately 0.45 LL. In subsequent
experiments, the maximal distance between the interactants could be
increased to 60 to 80
and the pore size reduced to an average size of
0.1 [A, although in both extremes induction was already definitely
weakened (Grobstein, 1957; Grobstein and Dalton, 1957). Electron
micrographs of filters with pores of the smallest size still allowing induction showed virtually no cytoplasmic penetration into the pores, suggesting a transmissible factor (s) responsible for the inductive effect. Experi-
253
of kidney tubules in the metanephrogenic mesenchyme. Our intention is
to summarize the main features of the induction of this differentiative
process and to review some of the subsequent events analyzed in our
laboratory.
A. Tissue Interaction in the Development of the Kidney Tubules
Early experimental work on kidney morphogenesis had suggested an
inductive effect exerted by the epithelial bud of the Wolffian duct. The
destruction of this led to failure of the metanephric blastema to differentiate into kidney tubules (Gruenwald, 1937, 1942, 1952). Clifford
Grobstein succeeded in separating these two intimately associated components, the epithelial bud and the metanephrogenic mesenchymal
blastema, in mouse embryos. During subsequent cultivation in vitro the
isolated metanephric blastema failed to differentiate, and so did the
epithelial ureteric bud when cultured alone. When these two tissue components were experimentally combined and grown together as an organ
culture, tubule formation was triggered in the metanephric blastema
(Grobstein, 1953, 1955a, 1959). The ureteric bud was not the only
structure able to induce tubule formation in the metanephrogenic blastema, but some other embryonic tissues seemed to possess a similar
stimulating capacity, like the "heterogenous" inductors known from
amphibian embryology. The most potent of these was the dorsal half of
the embryonic spinal cord, which has subsequently been employed in a
variety of experiments as an easily available and potent inductor. This
relatively unspecific nature of induction should always be borne in mind,
and even heterologous tissues (chick spinal cord) have been found to act
as inductors of tubule formation in mouse nephric blastema (Grobstein,
1955a).
The morphogenetic interaction between the mesenchyme and its
inductor does not require cell-to-cell contact between the interactants.
These can be separated by porous membrane filters, and Grobstein showed
in 1957 that the inductive effect can be transmitted over a distance of
20 to 30 [x and through pores of approximately 0.45 LL. In subsequent
experiments, the maximal distance between the interactants could be
increased to 60 to 80
and the pore size reduced to an average size of
0.1 [A, although in both extremes induction was already definitely
weakened (Grobstein, 1957; Grobstein and Dalton, 1957). Electron
micrographs of filters with pores of the smallest size still allowing induction showed virtually no cytoplasmic penetration into the pores, suggesting a transmissible factor (s) responsible for the inductive effect. Experi-