The Mouse fkh-2 Gene
IMPLICATIONS FOR NOTOCHORD, FOREGUT, AND MIDBRAIN REGIONALIZATION (*)
- Klaus H. Kaestner(1)(§),
- A. Paula Monaghan(1),
- Heidrun Kern(1),
- Siew-Lan Ang(3),
- Sandra Weitz(2),
- Peter Lichter(2) and
- Günther Schütz(1)
- From the (1) Division Molecular Biology of the Cell I and
- (2) Division Organization of Complex Genomes, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany and the
- (3) Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-LGME, INSERM U184, 67404 Illkirch, France
- § To whom correspondence should be addressed. Tel.: 49-6221-423411; Fax: 49-6221-423470.
Abstract
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-3β, 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-3β.
Footnotes
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↵* This work was supported by the Deutsche Forschungsgemeinschaft through SFB 229, the Fonds der Chemischen Industrie, and by European Community Grant number BI02-CT93-0319. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) X86368[GenBank].
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↵1 The abbreviation used are:
- HNF
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hepatocyte nuclear factor 3
- p.c.
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post-coitum.
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- Received July 12, 1995.
- Revision received September 28, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
