Erythroid cell development in fetal mice: Stabilization of the hemoglobin synthetic capacity

Abstract

Previous experiments on the total hepatic erythroid cell population during embryogenesis have demonstrated a shift from an unstable hemoglobin synthetic apparatus to a stabilized mechanism, relatively insensitive to inhibition by actinomycin of RNA synthesis, which occurs between the twelfth and thirteenth gestational days. The present studies examine this phenomenon at the cellular level, by means of quantitative radioautography of cells of each of the maturational stages of erythropoiesis during the unstable and the stabilized phases of hemoglobin synthesis. On fetal day 12, the uptake of leucine and iron by erythroblasts of all stages during maturation is uniformly suppressed by actinomycin. By the fifteenth day of gestation both polychromatophilic and orthochromatic erythroblasts have become resistant, and basophilic erythroblasts partially resistant, to the inhibitory effects of this antibiotic. In all other respects examined, including light and electron microscopic morphology, mitotic activity, RNA and protein synthesis, and sensitivity to the inhibition of RNA synthesis by actinomycin, the homologous cells on days 12 and 15 appear entirely comparable. These observations indicate that stabilization of the capacity for hemoglobin synthesis affects all stages of the erythroid cell series actively synthesizing hemoglobin. The data are incompatible with the hypothesis that stabilization of hemoglobin synthesis reflects the accumulation of larger numbers of more mature erythroblasts during embryonic development. The rate of hemoglobin synthesis is a maximum in polychromatophilic erythroblasts and this rate does not depend upon stabilization of the synthetic apparatus. Proerythroblasts appear predominantly engaged in the production of none-heme proteins, which are synthesized by an unstable mechanism at both gestational days. Stabilization of the capacity for hemoglobin synthesis most likely involves a decreased requirement for rate-limiting species of RNA. Factors in the fetal environment may be implicated in the development of a stable hemoglobin-synthetic apparatus.