DIFFERENTIATION OF KIDNEY MESENCHYME
285
at variance with those reported in the developing pancreas and some
other developmental models under similar conditions (Wessells, 1964b).
We cannot judge whether immediately preceding cell division is a
prerequisite for cells participating in the formation of the kidney tubules,
but it is clear that some of the cells in the tubule primordia resume
mitosis as tubule maturation and growth proceed. It may be that the
mechanism of tubule formation is intrinsically different from eytodifferentiation which is characterized by synthesis of specific macromolecules, as in the pancreas, mammary gland, and many other systems,
where terminal division takes place before the synthesis of special cell
products. At present the early condensations cannot be linked with any
"condensate-specific" synthetic product, although specific products are
synthesized later during the development of the tubules.
C. Macromolecular Synthesis and Morphogenesis
If tubule formation proves to be connected with the synthesis of
specialized proteins, attention will have to be turned to the metabolism
of nucleic acids and more specifically to RNA metabolism. The first
question is whether the first visible change, the formation of pretubular
condensates, is correlated with activation of genetic material, which
could then be analyzed with the aid of RNA metabolism according to the
current messenger doctrine. The answer to this seems to be in the affirmative. Total RNA synthesis, as measured by the uptake of specific precursors, increased sharply at 20 hours of cultivation and reached a peak
level at about 30 hours of cultivation, which coincided with the first
appearance of the condensates. Analysis of the different RNA classes at
this time showed that the quantitative increases, when compared to the
uninduced mesenchyme, was largely due to the synthesis of rRNA and
DNA-like RNA (Fig. 10). Electron microscopic observations lent further
support to the idea of the synthesis of ribosomal components. Aggregating cells displayed an increase of the polysomes in the cytoplasm (see
Section III,A).
However, the abrupt change in RNA metabolism prior to and at the
time of tubule formation does not prove the existence of a causal relationship between these two phenomena. Evidence for this was obtained from
the experiments with actinomycin. Actinomycin in low doses, if given
before 24 hours of incubation of the culture, prevented condensate formation. After this time it is no longer able to prevent morphological differentiation of tubules. Analogous situations have been reported with other
developing systems, such as the pancreas (Wessells, 1964c; Wessells and
285
at variance with those reported in the developing pancreas and some
other developmental models under similar conditions (Wessells, 1964b).
We cannot judge whether immediately preceding cell division is a
prerequisite for cells participating in the formation of the kidney tubules,
but it is clear that some of the cells in the tubule primordia resume
mitosis as tubule maturation and growth proceed. It may be that the
mechanism of tubule formation is intrinsically different from eytodifferentiation which is characterized by synthesis of specific macromolecules, as in the pancreas, mammary gland, and many other systems,
where terminal division takes place before the synthesis of special cell
products. At present the early condensations cannot be linked with any
"condensate-specific" synthetic product, although specific products are
synthesized later during the development of the tubules.
C. Macromolecular Synthesis and Morphogenesis
If tubule formation proves to be connected with the synthesis of
specialized proteins, attention will have to be turned to the metabolism
of nucleic acids and more specifically to RNA metabolism. The first
question is whether the first visible change, the formation of pretubular
condensates, is correlated with activation of genetic material, which
could then be analyzed with the aid of RNA metabolism according to the
current messenger doctrine. The answer to this seems to be in the affirmative. Total RNA synthesis, as measured by the uptake of specific precursors, increased sharply at 20 hours of cultivation and reached a peak
level at about 30 hours of cultivation, which coincided with the first
appearance of the condensates. Analysis of the different RNA classes at
this time showed that the quantitative increases, when compared to the
uninduced mesenchyme, was largely due to the synthesis of rRNA and
DNA-like RNA (Fig. 10). Electron microscopic observations lent further
support to the idea of the synthesis of ribosomal components. Aggregating cells displayed an increase of the polysomes in the cytoplasm (see
Section III,A).
However, the abrupt change in RNA metabolism prior to and at the
time of tubule formation does not prove the existence of a causal relationship between these two phenomena. Evidence for this was obtained from
the experiments with actinomycin. Actinomycin in low doses, if given
before 24 hours of incubation of the culture, prevented condensate formation. After this time it is no longer able to prevent morphological differentiation of tubules. Analogous situations have been reported with other
developing systems, such as the pancreas (Wessells, 1964c; Wessells and