The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nuclear Factor-3beta (HNF-3beta) are co-expressed in all three germ layers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation. In this paper, we have tested the possibility of functional synergism or redundancy between these two genes during embryogenesis by generating double-mutant mice for gsc and HNF-3beta. Double-mutant embryos of genotype gsc(−/−);HNF-3beta(+/−) show a new phenotype as early as embryonic days 8.75. Loss of Sonic hedgehog (Shh) and HNF-3beta expression was observed in the notochord and ventral neural tube of these embryos. These results indicate that gsc and HNF-3beta interact to regulate Shh expression and consequently dorsal-ventral patterning in the neural tube. In the forebrain of the mutant embryos, severe growth defects and absence of optic vesicles could involve loss of expression of fibroblast growth factor-8, in addition to Shh. Our results also suggest that interaction between gsc and HNF-3beta regulates other signalling molecules required for proper development of the foregut, branchial arches and heart.

Acampora
D.
,
Mazan
S.
,
Lallemand
Y.
,
Avantaggiato
V.
,
Maury
M.
,
Simeone
A.
,
Brulet
P.
(
1995
)
Forebrain and midbrain regions are deleted in Otx2/ mutants due to a defective anterior neuroectoderm specification during gastrulation.
Development
121
,
3279
3290
Ang
S.-L.
,
Wierda
A.
,
Wong
D.
,
Stevens
K. A.
,
Cascio
S.
,
Rossant
J.
,
Zaret
K. S.
(
1993
)
The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins.
Development
119
,
1301
1315
Ang
S.-L.
,
Conlon
R. A.
,
Jin
O.
,
Rossant
J.
(
1994
)
Positive and negative signals from mesoderm regulates the expression of mouse Otx2 in ectoderm explants.
Development
120
,
2979
2989
Ang
S.-L.
,
Rossant
J.
(
1994
)
HNF-3 is essential for node and notochord formation in mouse development.
Cell
78
,
561
574
Ang
S.-L.
,
Jin
O.
,
Rhinn
M.
,
Daigle
N.
,
Stevenson
L.
,
Rossant
J.
(
1996
)
A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain.
Development
122
,
243
252
Candia
A. H.
,
Hu
J.
,
Crosby
J.
,
Lalley
P. A.
,
Noden
D.
,
Nadeau
J. H.
,
Wright
C. V. E.
(
1992
)
Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos.
Development
116
,
1123
1136
Chiang
C.
,
Litingtung
Y.
,
Lee
K.
,
Young
K. E.
,
Corden
J. L.
,
Westphal
H.
,
Beach
P. A.
(
1996
)
Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function.
Nature
383
,
407
413
Collignon
J.
,
Varlet
I.
,
Robertson
E. J.
(
1996
)
Relationship between asymmetric nodal expression and the direction of embryonic turning.
Nature
381
,
155
158
Conlon
R. A.
,
Herrmann
B. G.
(
1993
)
Detection of messenger RNA by in situ hybridization to postimplantation embryo whole mounts.
Methods Enzymol
225
,
373
383
Crossley
P. H.
,
Martin
G. R.
(
1995
)
The mouse Fgf-8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo.
Development
121
,
439
451
Crossley
P. H.
,
Martinez
S.
,
Martin
G. R.
(
1996
)
Midbrain development induced by FGF8 in the chick embryo.
Nature
380
,
66
68
Couly
G.
,
Le Douarin
N. M.
(
1988
)
The fate map of the cephalic neural primordium at the presomitic to the 3-somite stage in the avian embryo.
Development
103
,
101
113
Davis
C. A.
,
Joyner
A. L.
(
1988
)
Expression patterns of the homeobox-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development.
Genes Dev
2
,
1736
1744
Davis
C. A.
,
Holmyard
D. P.
,
Millen
K. J.
,
Joyner
A. L.
(
1991
)
Examining pattern formation in mouse, chicken and frog embryos with an En-specific antiserum.
Development
111
,
287
298
Echelard
Y.
,
Epstein
D. J.
,
St-Jacques
B.
,
Shen
L.
,
Mohler
J.
,
McMahon
J. A.
,
McMahon
A. P.
(
1993
)
Sonic Hedgehog, a member of a family of putative signalling molecules, is implicated in the regulation of CNS polarity.
Cell
75
,
1417
1430
Gaunt
S. J.
,
Blum
M.
,
De Robertis
E.
(
1993
)
Expression of the mouse goosecoid gene during mid-embryogenesis may mark mesenchymal cell lineages in the developing head, limbs and body wall.
Development
117
,
769
778
Gradwohl
G.
,
Fode
C.
,
Guillemot
F.
(
1996
)
Restricted expression of a novel bHLH atonal-related protein to undifferentiated neural progenitors.
Dev. Biol
180
,
227
241
Hynes
M.
,
Poulsen
K.
,
Tessier-Lavigne
M.
,
Rosenthal
A.
(
1995
)
Control of neuronal diversity by the floor plate: Contact-mediated induction of midbrain dopaminergic neurons.
Cell
80
,
95
101
Izpisua-Belmonte
J. C.
,
De Robertis
E. M.
,
Storey
K. G.
,
Stern
C. D.
(
1993
)
The homeobox gene goosecoid and the origin of organizer cells in the early chick blastoderm.
Cell
74
,
645
659
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
Kelly
O. G.
,
Melton
D. A.
(
1995
)
Induction and patterning of the vertebrate nervous system.
Trends Genet
11
,
273
278
Laird
P. W.
,
Zijderveld
A.
,
Linders
K.
,
Rudnicki
M. A.
,
Jaenisch
R.
,
Berns
A.
(
1991
)
Simplified mammalian DNA isolation procedure.
Nucleic Acids Res
19
,
4293
–.
Lazzaro
D.
,
Price
M.
,
de Felice
M.
,
Di Lauro
R.
(
1991
)
The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain.
Development
113
,
1093
1104
Lee
S. M. K.
,
Danielian
P. S.
,
Fritzsch
B.
,
McMahon
A. P.
(
1997
)
Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain.
Development
124
,
959
969
Macdonald
R.
,
Barth
B. A.
,
Xu
Q.
,
Mikkola
I.
,
Wilson
S. W.
(
1995
)
Midline signalling is required for Pax gene regulation and patterning of eyes.
Development
121
,
3267
3278
Matsuo
I.
,
Kuratani
S.
,
Kimura
C.
,
Takeda
N.
,
Aizawa
S.
(
1995
)
Mouse Otx2 functions in the formation and patterning of rostral head.
Genes Dev
9
,
2646
2658
Monaghan
A. P.
,
Kaestner
K. H.
,
Grau.
E.
,
Schutz
G.
(
1993
)
Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm.
Development
119
,
567
578
Nornes
H. O.
,
Dressler
G. R.
,
Knapik
E. W.
,
Deutsch
U.
,
Gruss
P.
(
1990
)
Spatially and temporally restricted expression of Pax2 during murine neurogenesis.
Development
109
,
797
809
Oliver
G.
,
Mailhos
A.
,
Wehr
R.
,
Copeland
N. G.
,
Jenkins
N. A.
,
Gruss
P.
(
1995
)
Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development.
Development
121
,
4045
4055
Placzek
M.
(
1995
)
The role of the notochord and floor plate in inductive interactions.
Curr. Opin. Genet. Dev
5
,
499
506
Price
M.
,
Lemaistre
M.
,
Pischetola
M.
,
Di Lauro
R.
,
Duboule
D.
(
1991
)
A mouse gene related to Distal-less shows a restricted expression in the developing forebrain.
Nature
351
,
748
751
Rivera-Perez
J. A.
,
Mallo
M.
,
Gendron-Maguire
M.
,
Gridley
T.
,
Behringer
R. R.
(
1995
)
Goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development.
Development
121
,
3005
3012
Rubenstein
J. L.
,
Martinez
S.
,
Shimamura
K.
,
Puelles
L.
(
1994
)
The embryonic vertebrate forebrain: the Prosomeric model.
Science
266
,
578
580
Shawlot
W.
,
Behringer
R. R.
(
1995
)
Requirement for Lim1 in head-organizer function.
Nature
374
,
425
430
Shimamura
K.
,
Hartigan
D. J.
,
Martinez
S.
,
Puelles
L.
,
Rubenstein
J. L.
(
1995
)
Longitudinal organization of the anterior neural plate and neural tube.
Development
121
,
3923
3933
Simeone
A.
,
Gulisano
M.
,
Acampora
D.
,
Stornaiuolo
A.
,
Rambaldi
M.
,
Boncinelli
E.
(
1992
)
Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex.
EMBO J
11
,
2541
2550
Simeone
A.
,
Acampora
D.
,
Mallamaci
A.
,
Stornaiuolo.
A.
,
D'Apice.
M. R.
,
Nigro
V.
,
Boncinelli
E.
(
1993
)
A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo.
EMBO J
12
,
2735
2747
Tanabe
Y.
,
Jessell
T. M.
(
1996
)
Diversity and pattern in the developing spinal cord.
Science
274
,
1115
1123
Tao
W.
,
Lai
E.
(
1992
)
Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain.
Neuron
8
,
957
966
Thisse
C.
,
Thisse
B.
,
Halpern
M.
,
Postlethwait
J.H.
(
1994
)
goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas.
Dev. Biol
164
,
420
429
Walther
C.
,
Gruss
P.
(
1991
)
Pax-6, a murine paired box gene, is expressed in the developing CNS.
Development
113
,
1435
1449
Weinstein
D. C.
,
Ruiz i Altaba
A.
,
Chen
W. S.
,
Hoodless
P.
,
Prezioso
V.R.
,
Jessell
T.M.
,
Darnell
J. E.
Jr
(
1994
)
The winged-helix transcription factor HNF-3 is required for notochord development in the mouse embryo.
Cell
78
,
575
588
Wilkinson
D. G.
,
Bhatt
S.
,
Cook
M.
,
Boncinelli
E.
,
Krumlauf
R.
(
1989
)
Segmental expression of Hox-2 homeobox genes in the developing mouse hindbrain.
Nature
341
,
405
409
Xuan
S.
,
Baptista
C. A.
,
Balas
G.
,
Tao
W.
,
Soares
V. C.
,
Lai
E.
(
1994
)
Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres.
Neuron
14
,
1141
1152
Yamada
G.
,
Mansouri
A.
,
Torres
M.
,
Stuart
E. T.
,
Blum
M.
,
Schultz
,
De Robertis
E. M.
,
Gruss
P.
(
1995
)
Targeted mutation of the murine goosecoid gene results in craniofacial defects and prenatal death.
Development
121
,
2917
2922
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