POSTIMPLANTATION EXPRESSION PATTERNS INDICATE A ROLE FOR THE MOUSE FORKHEAD HNF-3 ALPHA,BETA AND GAMMA GENES IN DETERMINATION OF THE DEFINITIVE ENDODERM, CHORDAMESODERM AND NEUROECTODERM/

The HNF-3 alpha, beta and gamma genes constitute a family of transcrip tion factors that are required for hepatocyte-specific gene expression of a number of genes, e.g. transthyretin, alpha-1 antitrypsin and tyr osine aminotransferase. These genes share a highly conserved DNA-bindi ng domain first found in the Drosophila gene, forkhead, which is requi red for the normal patterning of the developing gut and central nervou s system in Drosophila. In adult mouse tissues, transcripts from HNF-3 alpha and beta have been localised to the liver, intestine and lung, whereas HNF-3 gamma is found in the liver, intestine and testis. In li ght of the early developmental significance of forkhead in drosophila, we have compared the patterns of expression of HNF-3 alpha, beta and gamma mRNAs during murine embryogenesis. We find that these genes are sequentially activated during development in the definitive endoderm. HNF-3 beta mRNA is expressed in the node at the anterior end of the pr imitive streak in all three germ layers and is the first gene of this family to be activated. Subsequently, HNF-3 alpha is transcribed in th e primitive endoderm in the region of the invaginating foregut and HNF -3 gamma appears upon hindgut differentiation. These genes have differ ent anterior boundaries of mRNA expression in the developing endoderm and transcripts are found in all endoderm-derived structures that diff erentiate posterior to this boundary. Therefore, we propose that these genes define regionalisation within the definitive endoderm. Furtherm ore, differential mRNA expression of HNF-3 alpha and beta is detected in cells of the ventral neural epithelium, chordamesoderm and notochor d. In the neural epithelium, expression of HNF-3 alpha and beta mRNA b ecomes localised to cells of the boor plate. We propose that, in addit ion to their characterised requirement for liver-specific gene express ion, HNF-3 alpha and beta are required for mesoderm and neural axis fo rmation. We also conclude that HNF-3 beta is the true orthologue of th e Drosophila forkhead gene.