Erythropoiesis in the mouse begins with the production of a distinct population of red blood cells in the blood islands of the visceral yolk sac at day

Erythropoiesis in the mouse begins with the production of a distinct population of red blood cells in the blood islands of the visceral yolk sac at day 7.5 postcoitum (p.c.). These primitive yolk sac red blood cells are large (about four times the volume of adult erythrocytes), nucleated and produce a distinctive set of embryonic hemoglobins (Craig and Russell, 1964; Russell and Bernstein, 1966; Barker, 1968; Chui et al., 1978). By day 11.5 p.c., there is a major transition in which these nucleated red blood cells diminish in number and the fetal liver becomes the major hematopoietic organ. Among the hepatic epithelial cells, erythroid precursors (erythroblasts) proliferate, differentiate and enter the circulation. The liver-derived, circulating erythrocytes (called definitive erythrocytes) are small, lack nuclei and express a distinctive set of adult hemoglobins, which continue to be synthesized in the adult organs of hematopoiesis, the spleen and bone marrow (Kovach et al., 1967; Fantoni et al., 1967; Gilman and Smithies, 1968; Barker, 1968; Rifkind et al., 1969; Wong et al., 1983). The switch from embryonic to adult hemoglobins has long been recognized by the distinctive electrophoretic mobilities of the hemoglobins derived from primitive and definitive erythrocytes. In vitro culture experiments promoted the notion that there are two hematopoietic progenitor cells, one producing embryonic and the other, adult hemoglobin (Wong et al., 1986). If indeed there are two progenitor cell types, then both must originate in the yolk sac. This is so since cultured primitive erythrocytes derived from the embryo before the fetal liver is formed can synthesize adult hemoglobins (Cudennec et al., 1981; Wong et al., 1982). Another method of following globin gene expression in early erythrocyte progenitor cells is to use in situ hybridization with gene-specific riboprobes. In this way, globin transcripts can be identified from the very onset of erythropoiesis and the ‘switching’ event can be pinpointed accurately, thereby documenting the stage at which embryonic globin gene expression is replaced by that of the adult. Here we have used this approach to study the expression of the α-globin gene cluster. The hemoglobin molecule is a heme-bearing tetramer made up of two heterodimeric subunits, each composed of an α or α-like chain and a β or β-like chain. In the mouse, the β globin gene cluster resides on chromosome 7 and consists of three embryonic and two adult genes (in addition to two pseudogenes) (Leder et al., 1980; Edgell et al., 1981; Hansen et al., 1982; Hill et al., 1984). The α-globin cluster, which resides on chromosome 11, consists of one 1041 Development 116, 1041-1049 (1992) Printed in Great Britain © The Company of Biologists Limited 1992