Visceral endoderm specification, role in the development of the pregastrulating embryo

Genetic and molecular evidence indicates that visceral endoderm, an extraem bryonic lineage derived from primitive endoderm, is required for gastrulati on, early anterior neural patterning, cell death and specification of poste rior mesodermal cell fares. vHNF1, a homeodomain containing transcription f actor belonging to the Hepatocyte Nuclear Factor (HNF) family, is first exp ressed in the primitive endoderm and is required for early embryogenesis an d plays an essential role in visceral endoderm specification. Homozygous mu tant embryos die just after implantation and before gastrulation displaying growth retardation, disorganise ectoderm and absence of visceral endoderm. Homozygous null blastocysts and differentiated embryonic stem cells do not express early or late visceral endoderm markers. Aggregation of vHnf1-defi cient embryonic stem cells with wildtype tetraploid embryos rescues the per iimplantation lethality and allows development to progress to early organog enesis, confirming that the early embryonic lethal phenotype is essentially due to defective extraembryonic tissue formation. These results, together with observations of other mutations affecting visceral endoderm function, in particular Hnf-4 alpha, indicate that the specification of the visceral endoderm involves a complex regulatory network rather than a linear cascade .