HNF-3 beta as a regulator of floor plate development.
The transcription factor gene HNF-3 beta is expressed in the ventral midline of the mouse embryonic neural tube, including the floor plate, a structure important for dorsoventral patterning and axonal guidance. To assess HNF-3 beta function, the gene has been ectopically expressed in the midbrain/hindbrain of transgenic embryos using an En-2 promoter/enhancer. By 18.5 days postcoitum, transgenic brains show a range of abnormalities, including absent inferior colliculus and reduced cerebellum. Earlier, several genes normally expressed in the floor plate (BMP-1, Steel factor, and HNF-3 alpha) are induced within the same ectopic dorsal domain as HNF-3 beta, and autoactivation of the endogenous HNF-3 beta is observed. Conversely, expression of the dorsal gene Pax-3 is suppressed. Ectopic dorsal neuronal differentiation and abnormal dorsal axonal projections are also seen. These results suggest that HNF-3 beta is an important regulator of floor plate development in vivo.
Sasaki
H
H
Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175.
Hogan
B L
BL
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology; D001483:Base Sequence; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004622:Embryo, Mammalian / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005091:Exons; D015870:Gene Expression; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D051542:Hepatocyte Nuclear Factor 3-beta; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011817:Rabbits; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; C496503:Foxa2 protein, mouse; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D005914:Globins