Otx2, a mouse homolog of the Drosophila orthodenticle gene, is first widely expressed in the epiblast but becomes progressively restricted to the anterior third of the embryo by the headfold stage. This progressive restriction correlates with the anterior migration of mesoderm in the embryo, suggesting that interactions with mesoderm may be involved in setting up the anterior domain of Otx2 expression in vivo. Using explant-recombination assays, we have obtained evidence that a positive signal from anterior mesendoderm is required to stabilize expression of Otx2 in vivo, whereas a negative signal from the later-forming posterior mesendoderm represses Otx2 expression in the posterior part of the embryo. We have also found that exogenous retinoic acid can mimic the effect of this negative signal and reduces the anterior domain of Otx2 expression.
REFERENCES
Adam
M. D.
, Dubnick
M.
, Kerlavage
A. R.
, Moreno
R.
, Kelley
J. M.
, Utterback
T. R.
, Nagle
J. W.
, Fields
J. W.
, Venter
J. C.
(1992
) Sequence identification of 2,375 human brain genes.
Nature
355
, 632
–634
Albano
R. M.
, Arkell
R.
, Beddington
R. S. P.
, Smith
J. C.
(1994
) Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expression of follisatin in primitive streak, somites and hindbrain.
Development
120
, 803
–813
Ang
S.-L.
, Rossant
J.
(1993
) Anterior mesendoderm induces mouse Engrailed genes in explant cultures.
Development
118
, 139
–149
Ang
S.-L.
, Wierda
A.
, Wong
D.
, Stevens
K. A.
, Cascio
S.
, Rossant
J.
, Zaret
K.
(1993
) The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/ forkhead proteins.
Development
119
, 1301
–1315
Beddington
R. S. P.
, Morgenstein
J.
, Land
H.
, Hogan
A.
(1989
) An in situ transgenic enzyme marker for the midgestation mouse embryo and the visualization of the inner cell mass clones during early organogenesis.
Development
106
, 37
–46
Blum
M.
, Gaunt
S. J.
, Cho
K. Y.
, Steinbesser
H.
, Blumberg
B.
, Bittner
D.
, De Robertis
E. M.
(1992
) Gastrulation in the mouse: the role of the homeobox gene goosecoid.
Cell
69
, 1097
–1106
Cohen
S. M.
, Jurgens
G.
(1990
) Gap-like segmentation genes that mediate Drosophila head developmnent.
Nature
346
, 482
–485
Conlon
R. A.
, Rossant
J.
(1992
) Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 gene in vivo.
Development
116
, 357
–358
Dalton
D.
, Chadwick
R.
, McGinnis
W.
(1989
) Expression and embryonic function of empty spiracles: a Drosophila homeobox gene with two patterning functions on the anterior-posterior axis of the embryo.
Genes Dev
3
, 1940
–1956
Fahrner
K.
, Hogan
B. L. M.
, Flavell
R. A.
(1987
) Transcription of H-2 and Qa genes in embryonic and adult mice.
EMBO J
6
, 1265
–1271
Finkelstein
R.
, Perrimon
N.
(1990
) The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila head developmnent.
Nature
346
, 485
–488
Finkelstein
R.
, Smouse
D.
, Theresa
M. C.
, Spradling
A. C.
, Perrimon
N.
(1990
) The orthodenticle gene encodes a novel homeo domain protein involved in the development of the Drosophila nervous system and ocellar visual structures.
Genes Dev
4
, 1516
–1527
Friedrich
G.
, Soriano
P.
(1991
) Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice.
Genes Dev
5
, 1513
–1523
Frohman
M. A.
, Boyle
M.
, Martin
G.
(1990
). Isolation of the mouse Hox 2.9 gene: analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm.
Development
110
, 589
–607
Gilbert
S. F.
, Saxen
L.
(1993
) Spemann's organizer: models and molecules.
Mech Dev
41
, 73
–89
Guillemot
F.
, Joyner
A.
(1993
) Dynamic expression of the murine achaete-scute homolog (MASH-1) in the developing nervous system.
Mech. Dev
42
, 171
–185
Hemmati-Brivanlou
A.
, Kelly
O. G.
, Melton
D. A.
(1994
) Follistatin, an antagonist of activin, is expressed in the Spemann Organizer and displays direct neuralizing activity.
Cell
77
, 283
–295
Herrmann
B. G.
(1991
) Expression pattern of the Brachury gene in whole-mount mutant embryos.
Development
113
, 913
–917
Hogan
B. L. M.
, Thaller
C.
, Eichele
G.
(1992
) Evidence that Hensen's node is a site of retinoic acid synthesis.
Nature
359
, 237
–241
Kessel
M.
, Gruss
P.
(1990
) Murine developmental control genes.
Science
249
, 314
–319
Kessel
M.
(1992
) Respecification of vertebral identities by retinoic acid.
Development
115
, 487
–501
Lamb
T. M.
, Knecht
A. K.
, Smith
W. C.
, Stachel
S. E.
, Economides
A. N.
, Stahl
N.
, Yancopoulous
G. D.
, Harland
R. M.
(1993
) Neural induction by the secreted polypeptide noggin.
Science
262
, 713
–718
Lawson
K. A.
, Meneses
J. J.
, Pedersen
R. A.
(1991
) Clonal analysis of epiblast fate during germ layer formation in the mouse embryo.
Development
113
, 891
–911
Marshall
H.
, Nonchev
S.
, Sham
M. H.
, Muchamore
I.
, Lumsden
A.
, Krumlauf
R.
(1992
) Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity.
Nature
360
, 737
–741
McGinnis
W.
, Krumlauf
R.
(1992
) Homeobox genes and axial patterning.
Cell
68
, 283
–302
Morriss-Kay
G. M.
, Murphy
P.
, Hill
R. E.
, Davidson
D. R.
(1991
). Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embros.
EMBO J
10
, 2985
–2995
Murphy
P.
, Hill
R.
(1991
). Expression of the mouse labial-like homeobox-containing genes, Hox 2.9 and Hox 1.6 during segmentation in the hindbrain.
Development
111
, 61
–74
Puelles
L.
, Rubenstein
L. R.
(1993
) Expression patterns of homeobox and other putative regulatory genes in the embryonic mouse forebrain suggest a neuromeric organization.
Trends NeuroSci
17
, 472
–479
Rossant
J.
, Zirnigibl
R.
, Cado
D.
, Shago
M.
, Giguere
V.
(1991
) Expression of a retinoic acid response element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis.
Genes Dev
5
, 1333
–1344
Simeone
A.
, Acampora
D.
, Gulisano
M.
, Stornaiuolo
A.
, Boncinelli
E.
(1992
) Nested expression domains of four homeobox genes in developing brain.
Nature
358
, 687
–690
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
Sive
H. L.
, Hattori
K.
, Weintraub
H.
(1989
) Progressive determination during formation of the anteroposterior axis in Xenopus laevis.
Cell
58
, 171
–180
Slack
J.
, Tannahill
D.
(1992
) Mechanism of anteroposterior axis specification in vertebrates. Lessons from amphibians.
Development
114
, 285
–302
Smith
W. C.
, Harland
R. M.
(1992
) Expression cloning of noggin, a new dorsalizing factor localized to the Spemann Organizer in Xenopus embryos.
Cell
70
, 829
–840
Smith
W. C.
, Knecht
A. K.
, Wu
M.
, Harland
R. M.
(1993
) Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm.
Nature
361
, 547
–549
Tam
P. P. L.
(1989
) Regionalization of the mouse embryonic ectoderm: allocation of prospective ectodermal tissues during gastrulation.
Development
107
, 55
–67
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
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