GOOSECOID AND HNF-3-BETA GENETICALLY INTERACT TO REGULATE NEURAL-TUBEPATTERNING DURING MOUSE EMBRYOGENESIS

The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nu clear Factor-3 beta (HNF-3 beta) are co-expressed in all three germ la yers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation. In this paper, we have tested the possibi lity of functional synergism or redundancy between these two genes dur ing embryogenesis by generating double-mutant mice for gsc and HNF-3 b eta. Double-mutant embryos of genotype gsc(-/-); HNF-3 beta(+/-) show a new phenotype as early as embryonic days 8.75, Loss of Sonic hedgeho g (Shh) and HNF-3 beta expression was observed in the notochord and ve ntral neural tube of these embryos. These results indicate that gsc an d HNF-3 beta interact to regulate Shh expression and consequently dors al-ventral patterning in the neural tube. In the forebrain of the muta nt embryos, severe growth defects and absence of optic vesicles could involve loss of expression of fibroblast growth factor-8, in addition to Shh, Our results also suggest that interaction between gsc and HNF- 3 beta regulates other signalling molecules required for proper develo pment of the foregut, branchial arches and heart.