Mesenchyme Fork Head-1 (MFH-1) is a forkhead (also called winged helix) transcription factor defined by a common 100-amino acid DNA-binding domain. MFH-1 is expressed in non-notochordal mesoderm in the prospective trunk region and in cephalic neural-crest and cephalic mesoderm-derived mesenchymal cells in the prechordal region of early embryos. Subsequently, strong expression is localized in developing cartilaginous tissues, kidney and dorsal aortas. To investigate the developmental roles of MFH-1 during embryogenesis, mice lacking the MFH-1 locus were generated by targeted mutagenesis. MFH-1-deficient mice died embryonically and perinatally, and exhibited interrupted aortic arch and skeletal defects in the neurocranium and the vertebral column. Interruption of the aortic arch seen in the mutant mice was the same as in human congenital anomalies. These results suggest that MFH-1 has indispensable roles during the extensive remodeling of the aortic arch in neural-crest-derived cells and in skeletogenesis in cells derived from the neural crest and the mesoderm.

Ang
S.-L.
,
Rossant
J.
(
1994
)
HNF-3is essential for node and notochord formation in mouse development.
Cell
78
,
561
574
Brannan
C.I.
,
Perkins
A.S.
,
Vogel
K.S.
,
Ratner
N.
,
Nordlund
M.L.
,
Reid
S.W.
,
Buchberg
A.M.
,
Jenkins
N.A.
,
Parada
L.F.
,
Copeland
N.G.
(
1994
)
Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues.
Genes Dev
8
,
1019
1029
Celoria
G.C.
,
Patton
R.B.
(
1959
)
Congenital absence of the aortic arch.
Am. Heart J
58
,
407
413
Christ
B.
,
Wilting
J.
(
1992
)
From somites to vertebral column.
Ann. Anat
174
,
23
32
Couly
G. F.
,
Coltey
P. M.
,
Le Douarin
N. M.
(
1993
)
The triple origin of skull in higher vertebrates: a study in quail-chick chimeras.
Development
117
,
409
429
Franz
T.
(
1989
)
Persistent truncus arteriosus in the Splotch mutant mouse.
Anat. Embryol
180
,
457
464
Goldmuntz
E.
,
Emanuel
B.S.
(
1997
)
Genetic disorders of cardiac morphogenesis: The DiGeorge and velocardiofacial syndromes.
Circ. Res
80
,
437
443
Hall
B. K.
,
Miyake
T.
(
1992
)
The membrane skeleton: the role of cell condensation in vertebrate skeletogenesis.
Anat Embryol
186
,
107
124
Hatini
V.
,
Huh
S.O.
,
Herzlinger
D.
,
Soares
V.C.
,
Lai
E.
(
1996
)
Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of winged helix transcription factor BF-2.
Genes Dev
10
,
1467
1478
Kaestner
K.H.
,
Bleckmann
S.C.
,
Monaghan
P.
,
Schlondorff
J.
,
Mincheva
A.
,
Lichter
P.
,
Schutz
G.
(
1996
)
Clustered arrangement of winged helix genes fkh-6 and MFH-1: possible implications for mesoderm development.
Development
122
,
1751
1758
Kaufmann
E.
,
Knochel
W.
(
1996
)
Five years on the wings of fork head.
Mech. Dev
57
,
3
20
Kessel
M.
,
Gruss
P.
(
1991
)
Homeotic transformation of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid.
Cell
67
,
89
104
Kirby
M.L.
,
Waldo
K.L.
(
1990
)
Role of neural crest in congenital heart disease.
Circulation
82
,
332
340
Kirby
M.L.
,
Waldo
K.L.
(
1995
)
Neural crest and cardiovascular patterning.
Circ. Res
77
,
211
215
Kurihara
Y.
,
Kurihara
H.
,
Oda
H.
,
Maemura
K.
,
Nagai
R.
,
Ishikawa
T.
,
Yazaki
Y.
(
1995
)
Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1.
J. Clin. Invest
96
,
293
300
Kurihara
Y.
,
Kurihara
H.
,
Suzuki
H.
,
Kodama
T.
,
Maemura
K.
,
Nagai
R.
,
Oda
H.
,
Kuwaki
T.
,
Cao
W.-H.
,
Kamada
N.
,
Jishage
K.
,
Ouchi
Y.
,
Azuma
S.
,
Toyoda
Y.
,
Ishikawa
T.
,
Kumada
M.
,
Yazaki
Y.
(
1994
)
Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1.
Nature
368
,
703
710
Lai
E.
,
Clark
K.L.
,
Burley
S.K.
,
Darnell
J.E.
Jr
(
1993
)
Hepatocyte nuclear factor 3/fork head or ‘winged helix’ proteins: A family of transcription factors of diverse biologic function.
Proc. Natl. Acad. Sci. USA
90
,
10421
10423
Mendelsohn
C.
,
Lohnes
D.
,
Decimo
D.
,
Lufkin
T.
,
LeMeur
M.
,
Chambon
P.
,
Mark
M.
(
1994
)
Function of the retinoic acid receptors (RARs) during development: (II) Multiple abnormalities at various stages of organogenesis in RAR double mutants.
Development
120
,
2749
2771
van Mierop
L.H.S.
,
Kutsche
L.M.
(
1984
)
Interruption of the aortic arch and coarctation of the aorta: Pathogenetic relations.
Am. J. Cardiol
54
,
829
834
Miura
N.
,
Iida
K.
,
Kakinuma
H.
,
Yang
X.-L.
,
Sugiyama
T.
(
1997
)
Isolation of the mouse (MFH-1) and human (FKHL14) Mesenchyme Fork Head-1 genes reveals conservation of their gene and protein structures.
Genomics
41
,
489
492
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
Mo
R.
,
Freer
A. M.
,
Zinyk
D. L.
,
Crackower
M. A.
,
Michaud
J.
,
Heng
H. H.-Q.
,
Chik
K. W.
,
Shi
X. M.
,
Tsui
L.-C.
,
Cheng
S. H.
,
Joyner
A. L.
,
Hui
C.-c.
(
1997
)
Specific and redundant functions of Gl2 and Gli3 zinc finger genes in skeletal patterning and development.
Development
124
,
113
123
Moller
J.H.
,
Edwards
J.E.
(
1965
)
Interruption of aortic arch.
Am. J. Roentgenol
95
,
557
572
Nehls
M.
,
Pfeifer
D.
,
Schorpp
M.
,
Hedrich
H.
,
Boehm
T.
(
1994
)
New member of the winged-helix protein family disrupted in mouse and rat nude mutations.
Nature
372
,
103
107
Noden
D. M.
(
1983
)
The role of the neural crest in patterning of avian skeletal, connective, and muscle tissues.
Dev. Biol
96
,
144
165
Olson
E.N.
,
Srivastava
D.
(
1996
)
Molecular pathways controlling heart development.
Science
272
,
671
676
Osumi-Yamashita
N.
,
Ninomiya
Y.
,
Doi
H.
,
Eto
K.
(
1994
)
The contribution of both forebrain and midbrain crest cells to the mesenchyme in the frontonasal mass of mouse embryos.
Dev. Biol
164
,
409
419
Sasaki
H.
,
Hogan
B. L. M.
(
1993
)
Differential expression of multiple forkhead related genes during gastrulation and axial pattern formation in the mouse embryo.
Development
118
,
47
59
Tanaka
T.
,
Akira
S.
,
Yoshida
K.
,
Umemoto
M.
,
Yoneda
Y.
,
Shirafuji
N.
,
Fujiwara
H.
,
Suematsu
S.
,
Yoshida
N.
,
Kishimoto
T.
(
1995
)
Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages.
Cell
80
,
353
361
Xuan
S.
,
Baptista
C.A.
,
Balas
G.
,
Tao
W.
,
Soares
V.C.
,
Lai
E.
(
1995
)
Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres.
Neuron
14
,
1141
1152
Weigel
D.
,
Jurgens
G.
,
Kuttner
F.
,
Seifert
E.
,
Jackle
H.
(
1989
)
The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo.
Cell
57
,
646
658
Weinstein
D.C.
,
Ruizi Altaba
A.
,
Chen
W.S.
,
Hoodles
P.
,
Prezioso
V.R.
,
Jassel
T.M.
,
Darnell
J.D.
Jr.
(
1994
)
The winged-helix transcription factor HNF-3 is required for notochord development in the mouse embryo.
Cell
78
,
575
588
Wilson
D.I.
,
Burn
J.
,
Scambler
P.
,
Goodship
J.
(
1993
)
DiGeorge syndrome: part of CATCH22.
J. Med. Genet
30
,
852
856
Winner
G. E.
,
Hargett
L.
,
Hogan
L. M.
(
1997
)
The winged helix transcription factor MFH1 is required for proliferation and patterning of paraxial mesoderm in the mouse embryo.
Genes Dev
11
,
926
940
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