The mouse fkh-2 gene. Implications for notochord, foregut, and midbrain regionalization.
The "winged helix" or "forkhead" transcription factors comprise a large gene family whose members are defined by a common 100-amino acid DNA binding domain. Here we describe the structure and expression of the mouse fkh-2 gene, which encodes a protein of 48 kDa with high similarity to other winged helix transcription factors within the DNA binding region, but unique potential transactivation domains. The gene is encoded by a single exon and is expressed in headfold stage embryos in the notochord, the anterior neuroectoderm, and a few cells of the definite endoderm. This expression becomes restricted to the anteriormost portions of the invaginating foregut and the developing midbrain. From day 11.5 of gestation onward, fkh-2 transcripts are restricted to the midbrain and become progressively localized to the red nuclei as the sole site of expression. The fkh-2 gene maps to chromosome 19B and is a candidate gene for the mouse mutation mdf (muscle-deficient) which is characterized by nervous tremors and degeneration of the hindlimb muscles. Although the expression patterns of the fkh-2 gene and another winged helix protein, HNF-3 beta, are overlapping in early stages of gestation and although the promoter of the fkh-2 gene contains a HNF-3 binding site, we demonstrate that the activation of the fkh-2 gene is independent of HNF-3 beta.
Division Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
K H
KH
Kaestner
A P
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Monaghan
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H
Kern
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SL
Ang
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S
Weitz
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P
Lichter
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G
Schütz
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004064:Digestive System / Q000196:embryology / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D005314:Embryonic and Fetal Development; D004707:Endoderm / Q000378:metabolism; D005091:Exons; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D005865:Gestational Age; D017403:In Situ Hybridization; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009672:Notochord / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic
D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors