Early mouse endoderm is patterned by soluble factors from adjacent germ layers

Endoderm that forms the respiratory and digestive tracts is a sheet of appr oximately 500-1000 cells around the distal cup of an E7.5 mouse embryo. Wit hin 2 days, endoderm folds into a primitive gut tube from which numerous or gans will bud. To characterize the signals involved in the developmental sp ecification of this early endoderm, we have employed an in vitro assay usin g germ layer explants and show that adjacent germ layers provide soluble, t emporally specific signals that induce organ-specific gene expression in en doderm. Furthermore, we show that FGF4 expressed in primitive streak-mesode rm can induce the differentiation of endoderm in a concentration-dependent manner. We conclude that the differentiation of gastrulation-stage endoderm is directed by adjacent mesoderm and ectoderm, one of the earliest reporte d patterning events in formation of the vertebrate gut tube.