Hemoglobin switching in Rana/Xenopus erythroid heterokaryons: factors mediating the metamorphic hemoglobin switch are conserved.

Hemoglobin switching, which occurs in all classes of vertebrates as well as in certain invertebrates, is due to developmental regulation of different globin genes which are typically arranged in clustered families. By fusing erythroid cells of different developmental programs, trans-acting factors that regulate this switch in gene expression have been detected [Ramseyer et al. (1989): Dev Biol 133:262-271]. Adult erythroid cells of one anuran species, Xenopus laevis, were fused with tadpole erythroid cells of another frog, Rana catesbeiana, creating developmental erythroid heterokaryons that synthesize adult Rana globin mRNA and hemoglobins. The results show that factors from adult Xenopus erythroid cells are capable of inducing adult Rana globin gene expression in the Rana tadpole erythroid cell nucleus. We have used the cross-induction of adult Rana hemoglobin synthesis in these adult Xenopus/Rana tadpole erythroid heterokaryons to address two practical questions, answers to which may be helpful in isolating developmental stage-specific globin gene regulatory proteins: 1) Are erythroblasts which are actively expressing globin mRNAs and hemoglobins richer in specific globin-inducing activities than other stages of erythroid cellular differentiation? 2) Do mature, circulating erythrocytes still have the activities necessary to mediate the cross-induction of Hb synthesis? The results reported here show that the answers to both questions are affirmative and show that quiescent, fully differentiated adult erythroid cells are still capable of expressing the trans-activator(s). These findings show that factors which mediate the metamorphic hemoglobin switch are conserved between these two genera of frogs.