Fig. 7. Fetal liver development requires hematopoietic cells but not c-Myc. (A) c-Myc expression in the fetal liver of E10.5 control (upper panel; higher magnification is shown in the right panel) and Sox2Cre;c-myc^flox/flox (bottom left) embryos. The broken line outlines the fetal liver. c-Myc is expressed in hepatoblasts (arrows) and blood cells (arrowheads). (B) Hematoxylin and Eosin (H&E) staining of control and Sox2Cre;c-myc^flox/flox fetal livers at E10.5. The top panels show low magnification, whereas the bottom panels show a high magnification. (C) HNF4 expression in control and Sox2Cre;c-myc^flox/flox embryos at E11.0. (D) H&E staining (top panels) and HNF4 expression (bottom panels) in E11.0 control and Tie2Cre;c-myc^flox/flox embryos. (E) Model illustrating the different direct roles for c-Myc in the midgestation embryo and the placenta. First, c-Myc is required to generate a functional embryonic placenta. Second, only in the presence of a normal placenta are the direct roles of c-Myc in the embryo proper revealed. Primitive YS erythropoiesis is drastically decreased. Although definitive AGM derived HSCs are generated in normal numbers, these mutant HSCs are non-functional and only very few hematopoietic cells (of primitive and definitive origin) reach the fetal liver, which as a consequence remains hypoplastic and fails to expand. All other organs and tissues proliferate and develop normally.