90
FRED H. WILT
DNA. Differentiation is brought about by application of control mechanisms, mutually interacting, that lead to specific biosynthesis in particular places at particular times. The controls are probably several, and
although ultimately based on molecular events, they operate at all levels
of organization—cell, tissue, and organism.
The erythropoietic tissue possesses many advantages for study of
control mechanisms regulating differentiation. Its characteristic cell type,
the red blood cell, is well defined, and the principal protein, hemoglobin
(Hb), is probably the best characterized protein of metazoa. It is the
general purpose of this article to focus attention on the differentiation
of erythropoietic tissue. It is not intended to fully review Hb and
erythrocyte formation. Rather, recent experiments will be selected to
illustrate the current understanding of what controls the initiation of
Hb synthesis, and the main attention will be directed to studies of the
chick and amphibian embryo.
II. Formation of Hemoglobin
A. Erythropoiesis
The normal stages of erythropoiesis in adult mammals and birds have
been thoroughly described, and the details are not necessary at this
juncture (cf. Maximow and Bloom, 1957; Lucas and Jamroz, 1961). In
brief, a stem cell in the bone marrow, termed a hemocytoblast, gives rise
to progeny which continue to divide for a time and synthesize large
amounts of hemoglobin. The usual stages are: hemocytoblast —» proerythroblast —> basophilic erythroblast -» polychromatic erythroblast —»
normoblast (or orthochromatic cell) —» reticulocyte —» erythrocyte. Nuclear extrusion occurs in mammals after the normoblast stage is reached,
and of course, subsequent cell division is then impossible.
It is known that the rate of hematopoiesis in adults is influenced by
the hormone, erythropoietin, and recent evidence on its mechanism of
action has been reviewed by Lange and Pavlovic-Kentera (1964).
Grasso et al. (1963) followed the developmental transitions in the fetal
rabbit by autoradiographic and cytospectrophotometric techniques. They
found both diploid and tetraploid DNA levels in cells prior to the
normoblast stage, but nucleated cells of subsequent stages contained
only diploid levels of DNA; this supports the usual view that normoblasts do not undergo mitosis. RNA synthesis was detected until the
end of the basophilic erythroblast stage, although the total RNA content per cell fell progressively from the hemocytoblast stage until it was
undetectable in the mature erythrocyte. The total cytoplasmic protein
per cell fell threefold between the stem cell and polychromatic stage, but
thereafter rose again because of a high level of Hb synthesis. The most
FRED H. WILT
DNA. Differentiation is brought about by application of control mechanisms, mutually interacting, that lead to specific biosynthesis in particular places at particular times. The controls are probably several, and
although ultimately based on molecular events, they operate at all levels
of organization—cell, tissue, and organism.
The erythropoietic tissue possesses many advantages for study of
control mechanisms regulating differentiation. Its characteristic cell type,
the red blood cell, is well defined, and the principal protein, hemoglobin
(Hb), is probably the best characterized protein of metazoa. It is the
general purpose of this article to focus attention on the differentiation
of erythropoietic tissue. It is not intended to fully review Hb and
erythrocyte formation. Rather, recent experiments will be selected to
illustrate the current understanding of what controls the initiation of
Hb synthesis, and the main attention will be directed to studies of the
chick and amphibian embryo.
II. Formation of Hemoglobin
A. Erythropoiesis
The normal stages of erythropoiesis in adult mammals and birds have
been thoroughly described, and the details are not necessary at this
juncture (cf. Maximow and Bloom, 1957; Lucas and Jamroz, 1961). In
brief, a stem cell in the bone marrow, termed a hemocytoblast, gives rise
to progeny which continue to divide for a time and synthesize large
amounts of hemoglobin. The usual stages are: hemocytoblast —» proerythroblast —> basophilic erythroblast -» polychromatic erythroblast —»
normoblast (or orthochromatic cell) —» reticulocyte —» erythrocyte. Nuclear extrusion occurs in mammals after the normoblast stage is reached,
and of course, subsequent cell division is then impossible.
It is known that the rate of hematopoiesis in adults is influenced by
the hormone, erythropoietin, and recent evidence on its mechanism of
action has been reviewed by Lange and Pavlovic-Kentera (1964).
Grasso et al. (1963) followed the developmental transitions in the fetal
rabbit by autoradiographic and cytospectrophotometric techniques. They
found both diploid and tetraploid DNA levels in cells prior to the
normoblast stage, but nucleated cells of subsequent stages contained
only diploid levels of DNA; this supports the usual view that normoblasts do not undergo mitosis. RNA synthesis was detected until the
end of the basophilic erythroblast stage, although the total RNA content per cell fell progressively from the hemocytoblast stage until it was
undetectable in the mature erythrocyte. The total cytoplasmic protein
per cell fell threefold between the stem cell and polychromatic stage, but
thereafter rose again because of a high level of Hb synthesis. The most