DIFFERENTIATION OF KIDNEY MESENCHYME
287
with new genomic activation in the sense of DNA transcription in
mRNA. Rutter et al. (1967) have presented a theory postulating three
levels of regulation in the synthesis of cellular proteins during differentiation. They postulate that at the first level, which they call protodifferentiation, the mRNA is transcribed, but not translated to any
appreciable extent into protein. In the second phase, overt differentiation,
large amounts of cell-specific protein are synthesized, utilizing the preformed mRNA. During this phase the protein-synthesizing machinery,
with the exception of the messenger, is organized. Finally, in the third
phase, the amount of specific synthesis is regulated to fit the needs of the
organism. One of the main events during the overt period of differentiation could be the synthesis and/or reorganization of the ribosomal system.
The results of the LDH isozyme shift can be explained in terms of this
theory. In the undifferentiated mesenchyme there are isozymes composed mainly of A subunits, but the existence of LDH-4 and LDH-3
shows that small amounts of B subunits are present (Fig. 11). The subsequent shift to the synthesis of more B subunits could signify an amplification of the translation of B subunits and thus represent the second
part—overt differentiation—of Rutter's scheme.
D. Stabilization of Differentiation
As suggested above, the formation of tubule primordia and some of
the biosynthetic activities in the tubules are in causal relationship. Does
this hold true of the more mature epithelial tubules also; in other words,
is the morphology of the tubules a prerequisite for the biochemical properties by which we have characterized them? If this is so, it would be
important to know the factors which maintain the organization of the
tubules. Grobstein and his associates (Kallman and Grobstein, 1964;
Grobstein and Cohen, 1965) have emphasized the role of the basement
membrane as a maintenance factor for newly formed epithelium. Accordingly, the changes in the spatial arrangement, the formation of the
junctional complexes, and the appearance of the basement membrane can
be considered as the visible criteria that ties have formed between the
tubule cells (see Section III,B,C).
The significance of structural organization of the tubules in the maintenance of the LDH isozyme pattern has been studied by Koskimies
(1967a,b,c). He could show that in the old cultures, in which the explants
begin to disintegrate and lose their tubular arrangement, the "adulttype" LDH pattern begins to change and returns to the pattern typical
of undifferentiated mesenchymes. Furthermore, when kidneys with the
287
with new genomic activation in the sense of DNA transcription in
mRNA. Rutter et al. (1967) have presented a theory postulating three
levels of regulation in the synthesis of cellular proteins during differentiation. They postulate that at the first level, which they call protodifferentiation, the mRNA is transcribed, but not translated to any
appreciable extent into protein. In the second phase, overt differentiation,
large amounts of cell-specific protein are synthesized, utilizing the preformed mRNA. During this phase the protein-synthesizing machinery,
with the exception of the messenger, is organized. Finally, in the third
phase, the amount of specific synthesis is regulated to fit the needs of the
organism. One of the main events during the overt period of differentiation could be the synthesis and/or reorganization of the ribosomal system.
The results of the LDH isozyme shift can be explained in terms of this
theory. In the undifferentiated mesenchyme there are isozymes composed mainly of A subunits, but the existence of LDH-4 and LDH-3
shows that small amounts of B subunits are present (Fig. 11). The subsequent shift to the synthesis of more B subunits could signify an amplification of the translation of B subunits and thus represent the second
part—overt differentiation—of Rutter's scheme.
D. Stabilization of Differentiation
As suggested above, the formation of tubule primordia and some of
the biosynthetic activities in the tubules are in causal relationship. Does
this hold true of the more mature epithelial tubules also; in other words,
is the morphology of the tubules a prerequisite for the biochemical properties by which we have characterized them? If this is so, it would be
important to know the factors which maintain the organization of the
tubules. Grobstein and his associates (Kallman and Grobstein, 1964;
Grobstein and Cohen, 1965) have emphasized the role of the basement
membrane as a maintenance factor for newly formed epithelium. Accordingly, the changes in the spatial arrangement, the formation of the
junctional complexes, and the appearance of the basement membrane can
be considered as the visible criteria that ties have formed between the
tubule cells (see Section III,B,C).
The significance of structural organization of the tubules in the maintenance of the LDH isozyme pattern has been studied by Koskimies
(1967a,b,c). He could show that in the old cultures, in which the explants
begin to disintegrate and lose their tubular arrangement, the "adulttype" LDH pattern begins to change and returns to the pattern typical
of undifferentiated mesenchymes. Furthermore, when kidneys with the