Synthesis of Embryonic Hemoglobins during Erythroid Cell Development in Fetal Mice

Three embryonic hemoglobins are formed in erythroid cells derived from yolk sac blood islands in fetal mice of the C57BL/6J strain. These cells provide a suitable model to study the rates of synthesis of specific proteins during the differentiation of cells. Erythroid cells differentiate initially in yolk sac blood islands from the 8th to the 10th day of gestation. (Fetal mice have a 20- to 21-day period of gestation.) These cells enter the fetal circulation and continue to develop as a relatively homogeneous population until Day 14 or 15, as indicated by a progressive decrease in the size of the nucleus, increasing pycnosis of nuclear chromatin, increasing content of hemoglobin in the cytoplasm, and decreasing content of ribosomes in the cytoplasm. The relative rates of synthesis of the three embryonic hemoglobins, Hb Ei, Hb Eii, and Hb Eiii, change as these erythroid cells differentiate. The synthesis of Hb Ei, the most abundant of the hemoglobins present at Day 10, decreases markedly after Day 11, while the synthesis of Hb Eii proceeds at a relatively linear rate over the entire period and by Day 12 is present in the largest amount. Hb Eiii is formed at a slower rate than Hb Ei or Hb Eii during the entire period from Day 10 to Day 14. Hemoglobin formation in yolk sac erythroid cells is not inhibited by actinomycin D from Day 10, while the antibiotic does inhibit RNA formation and non-heme protein synthesis in these cells. It is suggested that changes in rates of synthesis of the three embryonic hemoglobins which occur as yolk sac erythroid cells develop between Days 10 and 14 may be largely determined by factors regulating protein formation which do not require the immediate or continued synthesis of RNA.