Fig. 8. A model for patterning of the foregut endoderm through threshold of FGF activity. Schematic representation of embryo expression data shown in Figs 1 and 7, using sagittal cross-section through cardiac and foregut regions. (A) The onset of FGF2 expression in the five- to six-somite cardiac mesoderm (Jung et al., 1999) (data not shown) occurs just prior to albumin activation in the foregut endoderm, which predominantly expresses FGFR1. This threshold of FGF2 (broken arrow) is sufficient for liver but not lung induction. (B) Coincident with NKX2.1 activation in the seven- to eight-somite ventral endoderm, is the expansion of FGFR4 expression and the addition of FGF1 with FGF2 in the developing heart (Jung et al., 1999). The dose of FGF signaling (broken arrow) is now sufficient to induce lung specification, with frequent co-expression of NKX2.1 and albumin in the same cells. Broken arrows reflect that induction of liver and lung by cardiac signaling may be direct or indirect (see Discussion). Endogenous FGF2 in the adjacent notochord (arrow) may induce albumin expression in dorsal foregut endoderm. High doses of FGF, inhibitory to albumin in vitro, could contribute to refinement of cell commitment (C). Functional data (Fig. 7) indicates that induction of NKX2.1, but not albumin, relies on intact FGFR4 activity. (C) Once cell specification occurs, presumed positive and negative feedback between neighboring germ layers, including the mesenchyme of the septum transversum, maintain and refine cell commitment. Dark red indicates cardiac region.