The ‘winged helix’ or ‘forkhead’ transcription factor gene family is defined by a common 100 amino acid DNA binding domain which is a variant of the helix-turn-helix motif. Here we describe the structure and expression of the mouse fkh-6 and MFH-1 genes. Both genes are expressed in embryonic mesoderm from the headfold stage onward. Transcripts for both genes are localised mainly to mesenchymal tissues, fkh-6 mRNA is enriched in the mesenchyme of the gut, lung, tongue and head, whereas MFH-1 is expressed in somitic mesoderm, in the endocardium and blood vessels as well as the condensing mesenchyme of the bones and kidney and in head mesenchyme. Both genes are located within a 10 kb region (in mouse chromosome 8 at 5.26 +/− 2.56 cM telomeric to Actsk1. The close physical linkage of these two winged helix genes is conserved in man, where the two genes map to chromosome 16q22-24. This tandem arrangement suggests the common use of regulatory mechanisms. The fkh-6/MFH-1 locus maps close to the mouse mutation amputated, which is characterised by abnormal development of somitic and facial mesoderm. Based on the expression patterns we suggest that a mutation in MFH-1, not fkh-6 is the possible cause for the amputated phenotype.

Reference

Ang
S.-L.
,
Wierda
A.
,
Wong
D.
,
Stevens
K. A.
,
Cascio
S.
,
Rossant
J.
,
Zaret
K. S.
(
1993
)
The formation and maintenance of the definite endoderm lineage in the mouse: involvement of HNF-3/ fork head proteins.
Development
119
,
1301
1315
Ang
S.-L.
,
Rossant
J.
(
1994
)
HNF-3 is essential for node and notochord formation in mouse development.
Cell
78
,
561
574
Avraham
K. B.
,
Prezioso
V. R.
,
Chen
W. S.
,
Lai
E.
,
Sladek
F. M.
,
Zhong
W.
,
Darnell
J. E.
,
Jenkins
N. A.
,
Copeland
N. G.
(
1992
)
Murine chromosomal localization of four hepatocyte-enriched transcription factors: HNF-3, HNF-3, HNF-3and HNF-4.
Genomics,
13
,
264
268
Avraham
K. B.
,
Fletcher
C.
,
Overdier
D. G.
,
Clevidence
D. E.
,
Lai
E.
,
Costa
R. H.
,
Jenkins
N. A.
,
Copeland
N. G.
(
1995
)
Murine chromosomal localization of eight members of the hepatocyte nuclear factor 3/fork head winged helix family of transcription factors.
Genomics
25
,
388
393
Bassel-Duby
R.
,
Hernandez
M. D.
,
Yang
Q.
,
Rochelle
J. M.
,
Seldin
M. F.
,
Williams
R. S.
(
1994
)
Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes.
Mol. Cell. Biol
14
,
4596
4605
Birchmeier
C.
,
Birchmeier
W.
(
1993
)
Molecular aspects of mesenchymal-epithelial interactions.
Annu. Rev. Cell Biol
9
,
511
540
Cadigan
K. M.
,
Grossniklaus
U.
,
Gehring
W. J.
(
1994
)
Functional redundancy: The respective roles of the two sloppy paired genes in Drosophil a segmentation.
Proc. Natl. Acad. Sci. USA
91
,
6324
6328
Chomczynski
P.
,
Sacchi
N.
(
1987
)
Single-step method of RNA isolation.
Analyt. Biochem
162
,
156
159
Church
G. M.
,
Gilbert
W.
(
1984
)
Genomic sequencing.
Proc. Natl. Acad. Sci. U. S. A
81
,
1991
1995
Clark
K. L.
,
Halay
E. D.
,
Lai
E.
,
Burley
S. K.
(
1993
)
Co-crystal structure of the HNF-3/ fork head DNA recognition motif resembles histone H5.
Nature,
364
,
412
420
Clevidence
D. E.
,
Overdier
D. G.
,
Peterson
R. S.
,
Porcella
A.
,
Ye
H.
,
Paulson
K. E.
,
Costa
R. H.
(
1994
)
Members of the HNF-3/forkhead family of transcription factors exhibit distinct cellular expression patterns in lung and regulate the surfactant protein B promoter.
Dev. Biol
166
,
195
209
Conlon
R. A.
,
Herrmann
B. G.
(
1993
)
Detection of messenger RNA by in situ hybridization to postimplantation embryo whole mounts.
Meth. Enzymol
225
,
373
383
Flint
O. P.
,
Ede
D. A.
(
1978
)
Facial development in the mouse; a comparison between normal and mutant (amputated) mouse embryos.
J. Embryol. exp. Morph
48
,
249
267
Flint
O. P.
,
Ede
D. A.
(
1982
)
Cell interactions in the developing somite: in vitro comparisons between amputated (am / am) and normal mouse embryos.
J. Embryol. exp. Morph
67
,
113
125
Grossniklaus
U.
,
Pearson
R. K.
,
Gehring
W. J.
(
1992
)
The Drosophilasloppy paired locus encodes two proteins involved in segmentation that show homology to mammalian transcription factors.
Genes Dev
6
,
1030
1051
Kaestner
K. H.
,
Ntambi
J. M.
,
Kelly
T. J.
,
Lane
M. D.
(
1989
)
Differentiation-induced gene expression in 3T3-L1 preadipocytes: a second differentially expressed gene encoding stearoyl-CoA desaturease.
J. Biol. Chem
264
,
14755
14761
Kaestner
K. H.
,
Lee
K.-H.
,
Schlöndorff
J.
,
Hiemisch
H.
,
Monaghan
A. P.
,
Schutz
G.
(
1993
)
Six members of the mouse forkhead gene family are develomentally regulated.
Proc. Natl. Acad. Sci. USA
90
,
7628
7631
Kaestner
K. H.
,
Hiemisch
H.
,
Luckow
B.
,
Schutz
G.
(
1994
)
The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence and mRNA distribution.
Genomics
20
,
377
385
Kaestner
K. H.
,
Monaghan
A. P.
,
Kern
H.
,
Ang
S.-L.
,
Weitz
S.
,
Lichter
P.
,
Schutz
G.
(
1995
)
The mouse fkh-2 gene: implications for notochord, foregut and midbrain regionalization.
J. Biol. Chem
270
,
30029
30035
Lai
E.
,
Clark
K. L.
,
Burley
S. K.
,
Darnell
J. E.
(
1993
)
Hepatocyte nucler factor 3/ fork head or ‘winged helix’ proteins: a family of transcription factors of diverse biological function.
Proc. Natl. Acad. Sci. USA
90
,
10421
10423
Lichter
P.
,
Chang Tang
C.-J.
,
Call
K.
,
Hermanson
G.
,
Evans
G. A.
,
Housman
D.
,
Ward
D. C.
(
1990
)
High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones.
Science
247
,
64
69
Miura
N.
,
Wanaka
A.
,
Tohyama
M.
,
Tanaka
K.
(
1993
)
MFH-1, a new member of the fork head domain family, is expressed in developing mesenchyme.
FEBS Lett
326
,
171
176
Monaghan
A. P.
,
Kaestner
K. H.
,
Grau
E.
,
Schutz
G.
(
1993
)
Postimplantation expression patterns indicate a role for the mouse fork head /HNF-3, andgenes in determination of the definite endoderm, chordamesoderm and neurectoderm.
Development
119
,
567
578
Overdier
D. G.
,
Porcella
A.
,
Costa
R. H.
(
1994
)
The DNA-binding specificity of the hepatocyte nucler factor 3/forkhead domain is influenced by amino acid residues adjacent to the recognition helix.
Mol. Cell. Biol
14
,
2755
2766
Pani
L.
,
Overdier
D. G.
,
Porcella
A.
,
Qian
X.
,
Lai
E.
,
Costa
R. H.
(
1992
)
Hepatocyte nucler factor 3contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein.
Mol. Cell. Biol
12
,
3723
3732
Sanger
F.
,
Nicklen
S.
,
Coulson
A. R.
(
1977
)
DNA sequencing with chain-terminating inhibitors.
Proc. Natl. Acad. Sci. U. S. A
74
,
5463
5467
Sasaki
H.
,
Hogan
B. L. M.
(
1993
)
Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo.
Development
118
,
47
59
Sasaki
H.
,
Hogan
B. L. M.
(
1994
)
HNF-3 as a regulator of floor plate development.
Cell
76
,
103
115
Tamura
T.
,
Sumita
K.
,
Fujino
J.
,
Aojama
A.
,
Horiskoshi
M.
,
Hoffmann
A.
,
Roeder
R. G.
(
1991
)
Striking homology of the ‘variable’ N-terminal as well as ‘conserved core’ domains of the mouse and human TATA-factors (TFIID).
Nucl. Acids Res
19
,
3861
3865
The European Backcross Collaborative Group
(
1994
)
Towards high resolution maps of the mouse and human genomes- a facility for ordering markers to 0. 1 cM resolution. Hum. Mol.
Genet
3
,
621
627
Weigel
D.
,
Jurgens
G.
,
Kuttner
F.
,
Seifert
E.
,
Jäckle
H.
(
1989
)
The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo.
Cell
57
,
645
658
Weinstein
D. C.
,
Ruiz i Altaba
A.
,
Chen
W. C.
,
Hoodless
P.
,
Prezioso
V. R.
,
Jessell
T. M.
,
Darnell
J. E.
(
1994
)
The winged-helix transcription factor HNF-3 is required for notochord development in the mouse embryo.
Cell
78
,
575
588
Wiese
S.
,
Murphy
D. B.
,
Schlung
A.
,
Burfeind
P.
,
Schmundt
D.
,
Schnulle
V.
,
Mattei
M.-G.
,
Thies
U.
(
1995
)
The genes for human brain factor 1 and 2, members of the fork head gene family, are clustered on chromosome 14q.
Biochim. Biophys. Acta
1262
,
105
112
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