Goosecoid and HNF-3beta genetically interact to regulate neural tube patterning during mouse embryogenesis.
The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nuclear Factor-3beta (HNF-3beta) are co-expressed in all three germ layers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation. In this paper, we have tested the possibility of functional synergism or redundancy between these two genes during embryogenesis by generating double-mutant mice for gsc and HNF-3beta. Double-mutant embryos of genotype gsc(-/-);HNF-3beta(+/-) show a new phenotype as early as embryonic days 8.75. Loss of Sonic hedgehog (Shh) and HNF-3beta expression was observed in the notochord and ventral neural tube of these embryos. These results indicate that gsc and HNF-3beta interact to regulate Shh expression and consequently dorsal-ventral patterning in the neural tube. In the forebrain of the mutant 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-3beta regulates other signalling molecules required for proper development of the foregut, branchial arches and heart.
Filosa
S
S
Institut de Génétique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur/Collège de France, Illkirch, CU de Strasbourg.
Rivera-Pérez
J A
JA
Gómez
A P
AP
Gansmuller
A
A
Sasaki
H
H
Behringer
R R
RR
Ang
S L
SL
D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000502:physiology*; D004064:Digestive System / Q000196:embryology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D005865:Gestational Age; D051956:Goosecoid Protein; D006133:Growth Substances / Q000502:physiology; D053823:Hedgehog Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009154:Mutation; D009420:Nervous System / Q000196:embryology*; D009672:Notochord / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D016548:Prosencephalon / Q000196:embryology; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; C496503:Foxa2 protein, mouse; D051956:Goosecoid Protein; D006133:Growth Substances; C497993:Gsc protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors