1 Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology,
2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
2 Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka,
Suita, Osaka 565-0871, Japan
3 Laboratory for Animal Resources and Genetic Engineering (LARGE), RIKEN Center
for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo
650-0047, Japan
Author for correspondence (e-mail:
sasaki{at}cdb.riken.jp)
Accepted 24 August 2005
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SUMMARY |
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Key words: Tead, Node, Foxa2, Notochord, Enhancer, Mouse
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Introduction |
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Analysis of lower vertebrates revealed the mechanisms of the initial stage
of organizer development. In zebrafish and Xenopus embryos, dorsal
activation of Wnt pathway followed by TGFß/nodal signaling was found to
promote organizer development (De Robertis
et al., 2000; Hibi et al.,
2002
; Moon and Kimelman,
1998
). In chick embryos, cooperation of these two signals
continuously activates organizer genes in cells passing through the anterior
end of the primitive streak (Joubin and
Stern, 1999
). The development of the EGO/MGO in mouse embryos may
also operate by a similar mechanism (Tam
and Gad, 2004
). However, little is known about the mechanism of
node formation and maintenance in mouse embryos.
Foxa2 (formerly known as HNF3ß) is a key transcription factor for the
development of midline signaling centers, including the gastrula organizer,
node, notochord and floor plate of the neural tube
(Ang and Rossant, 1994;
Sasaki and Hogan, 1994
;
Weinstein et al., 1994
) (see
Fig. S1 in the supplementary material). As part of an effort to analyze the
regulation of Foxa2 expression, we previously identified two
enhancers that drive gene expression in the node/notochord and the floor
plate, respectively (Sasaki and Hogan,
1996
). Analysis of the node/notochord enhancer in multiple species
led to the identification of an evolutionarily conserved sequence motif, CS3,
which is essential for enhancer activity
(Nishizaki et al., 2001
).
Here, we identified the Tead family transcription factors as proteins that
bind to CS3.
Tead family transcription factors all contain a DNA-binding domain called a
TEA domain, and consist of four members (Tead1-Tead4) in both mouse and human
(Jacquemin et al., 1998;
Kaneko and DePamphilis, 1998
).
The founding member of this family, Tead1 [also known as transcriptional
enhancer factor 1 (TEF-1)], was originally identified as an activator of
simian virus 40 (SV40) enhancer (Davidson
et al., 1988
; Xiao et al.,
1991
). A Drosophila Tead protein, Scalloped (Sd),
interacts with a co-activator protein, Vestigial (Vg), and regulates wing
development (Halder et al.,
1998
; Simmonds et al.,
1998
). Vertebrate Tead proteins also require co-factors to act as
activators, and the candidates are the four Vg homologs
(Maeda et al., 2002
;
Vaudin et al., 1999
) and
Yes-associated protein 65 (YAP65) (Maeda
et al., 2002
; Vassilev et al.,
2001
; Vaudin et al.,
1999
). Several other mechanisms are also suggested for regulation
of Tead activity, including interaction with other transcription factors and
modification by protein kinases (Gupta et
al., 2001
; Gupta et al.,
1997
; Jiang et al.,
2001
; Thompson et al.,
2003
). Tead genes are expressed widely, from
preimplantation embryos to various adult tissues, with distinct patterns
(Jacquemin et al., 1998
;
Kaneko et al., 1997
). Tead
proteins are suggested to be involved in activation of the cardiac and
skeletal muscle genes, CTP:phosphocholine cytidylyltransferase (Pcyt
Mouse Genome Informatics) and Pax3 in neural crest cells
(Jiang et al., 2000
;
Milewski et al., 2004
;
Stewart et al., 1994
;
Sugimoto et al., 2001
), and
Tead1 mutant embryos die between E11 and 12 due to resulting heart
defects (Chen et al., 1994
).
However, the roles played by Tead genes during early embryogenesis
have not yet been revealed.
In this study, we first showed that the core element (CE) of the Foxa2 enhancer drives gene expression in the node. Two transcription factors activate the CE in a cooperative fashion, and Tead proteins are one of these factors. The Tead-binding site in the CE was essential for node/notochord enhancer (NE) activity, and inhibition of Tead function in mouse embryos disturbed notochord development. In zebrafish embryos, manipulation of Tead activity changed the expression of foxa2. These results suggest that the key mechanism of Foxa2 expression in the node/notochord is activation of the enhancer core element in the node by Tead in cooperation with an unidentified transcription factor, and that a similar mechanism also operates in the embryonic shield of zebrafish.
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Materials and methods |
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Yeast one-hybrid screening
Yeast one-hybrid screening was performed using the MATCHMAKER One-Hybrid
System (Clontech) following the manufacturer's protocol. A tetramer of
double-stranded CE-oligonucleotide
5'-TTTGCAAGGAAGGGAGAAATTCCACCAc-3'
3'-gAAACGTTCCTTCCCTCTTTAAGGTGGT-5' was used as a target site, and
was cloned into the vectors pHisi-1 and pLacZi. Clones
(4.5x106) of a mouse 7-day embryo MATCHMAKER cDNA library
(Clontech) were screened in the presence of 10 mmol/l 3-aminotriazole. The
cDNA insert of the plasmid DNA was amplified from positive yeast colonies by
PCR, followed by sequence determination and BLAST search against the GenBank
database. Plasmid DNAs were recovered from representative clones for
subsequent analysis.
Gel mobility shift assay
Expression plasmids for Tead and Rel were constructed by cloning the coding
sequences of respective cDNAs into pcDNA3.1-His (Invitrogen) or pCMV/SV-Flag1
(Kamachi et al., 2000). Tead1
and Tead3 cDNAs were gifts from Dr H. Ohkubo
(Yasunami et al., 1996
). The
resulting plasmids were used for production of proteins via the TnT T7 coupled
reticulocyte lysate system (Promega). Gel mobility shift assay was performed
as described (Sasaki et al.,
1997
).
Transfection assay
Reporter plasmids were constructed by cloning the NE enhancer fragment or
eight copies of CE oligonucleotide sequences into p51-LucII
(Kamachi et al., 2000
). The
7xTcf-BS reporter and stabilized ß-catenin expression vector are
described (Takahashi et al.,
2000
; Ueda et al.,
2002
). Wnt expression plasmids were gifts from Dr S. Nakagawa
(Kubo et al., 2003
). The Yap65
expression plasmid was created by cloning the coding sequence of Yap65 into
pcDNA3. For transfection, P19 cells were plated into 6-well plates at a
density of 2x105 cells/well 4 hours before transfection. A
mixture of Fugene 6 (Roche) and DNA consisting of effector (0.4 µg),
reporter (0.4 µg) and reference (pCS2-ß-gal, 0.1 µg) was added to
the cells and was cultured for 14 to 48 hours, depending on experiments.
Preparation of lysates, luciferase and ß-galactosidase assays were as
described (Sasaki et al.,
1999
). Luciferase activities were normalized by
ß-galactosidase activities.
In situ hybridization
In situ hybridization of whole-mount tissue or paraffin sections of mouse
and zebrafish embryos was performed as described previously
(Henrique et al., 1995;
Nikaido et al., 1997
;
Wilkinson, 1992
).
Electroporation
Electroporation and in vitro culture of mouse embryos were performed based
on procedures described previously
(Davidson et al., 2003;
Sturm and Tam, 1993
). Briefly,
each embryo was soaked in a 10-µl drop of Tyrode's Ringer solution
containing pDISP-SEAP (an expression vector for the membrane-tethered form of
human placental alkaline phosphatase; a gift from Dr T. Yamamoto) and either
pCS2-Tead2-EnR or pCS2 (0.5 µg/µl each) for 10 minutes, followed by
electroporation with five pulses of 15V for 50 mseconds using a square-wave
pulse generator (CUY-21; BEX). The distance between electrodes was 3 mm. After
16 hours' culture, embryos were stained for both ß-galactosidase and
alkaline phosphatase activities (Itasaki
et al., 1996
).
Zebrafish embryos
Wild-type zebrafish (Danio rerio) embryos were obtained from
natural crosses of fish with the AB/India genetic background. Capped mRNAs,
prepared as previously described (Koshida
et al., 1998; Makita et al.,
1998
), were diluted to the appropriate concentration with MilliQ
water containing 0.05% Phenol Red and injected into 1-cell embryos.
Approximately 400-500 pl of RNA was injected into each embryo.
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Results |
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Two transcription factors cooperate in the activation of the CE by ß-catenin and in gene expression in the node and notochord
As the CE is activated efficiently in Wnt/ß-catenin-treated P19 cells,
we used this system to analyze the mechanism of CE activation. For this
purpose we first studied the effect of altering the CE sequence on its
activation in P19 cells. The CE mutants (M1, M2, M3, M4 and M5) are
evenly-spaced trinucleotide mutants spanning the CE and beginning at its
5' end (Fig. 3A). Two
disjunct mutations, M1 and M4, abolished activation, while the others had
little or no effect on activation rate and/or basal expression
(Fig. 3B). As confirmation, an
additional mutant, M1-2, also failed to respond to ß-catenin, confirming
the importance of the 5' flanking region of CE
(Fig. 3A,B). These results
suggest that two transcription factors bind to the CE to activate it. To
understand the relationship between these two transcription factors, we
altered the distance between the two binding sites by inserting four or six
nucleotides between them (ins4 and ins6:
Fig. 3A). These alterations
significantly reduced ß-catenin-mediated activation of the CE
(Fig. 3B), indicating the
importance of the distance and/or topological relationship between the binding
sites.
To understand the functional significance of these binding sites for in
vivo gene expression, we constructed mutant enhancers containing the M1, M1-2
or M4 mutations, and tested their activities in ß-catenin-treated P19
cells. M1-2 and M4 mutated enhancers lost their activity, while the M1 mutated
enhancer was activated at a reduced level (data not shown). Thus, we selected
the M1-2 and M4 mutations as representative mutations canceling enhancer
activity in Wnt-treated P19 cells, and tested their effects on in vivo
enhancer activity. No transgenic embryos harboring M1-2 or M4 mutated
enhancers expressed the ß-galactosidase transgene in the node or
notochord (Fig. 3D,F; wild
type, Fig. 3C). Instead, the
ß-galactosidase expression pattern in these embryos displayed a modified
pattern, in that the transgene-expressing cells were confined to the
mediolateral portion of the posterior endoderm, resembling mutants with a
deletion of CS3 (Nishizaki et al.,
2001). Introduction of M3 and M5 mutations, which retained CE
activity in P19 cells, to the enhancer led to normal transgene expression in
the node/notochord (Fig. 3E,G).
Taken together, these results suggest that activation of the CE through the
cooperation of two transcription factors is essential for NE-mediated
Foxa2 gene expression in the node and notochord.
Identification of Tead as a CE-binding protein
To identify the transcription factors acting on the CE, we performed yeast
one-hybrid screening of an E7.0 mouse embryo cDNA library using the CE as a
probe. Among the 70 positive clones obtained, 34 clones encoded Tead4, three
clones encoded Tead2, and 22 clones encoded RelA. The remaining 11 clones did
not encode transcription factors, suggesting that they are pseudo-positives. A
gel mobility shift assay showed that Tead4 and Tead2 proteins bound to CE in a
sequence-specific manner, as shown by competition with an excess amount of
unlabeled CE oligonucleotide (Fig.
4A, lanes 2, 3, 10, 11). Competition with a series of unlabeled
mutant CEs (M1-M5, Fig. 3A)
showed that the M4 mutation abolished binding of Tead2/4
(Fig. 4A, lanes 4-8, 12-16).
Tead1 binds to the two unrelated sequence motifs of SV40 enhancers, GT-IIC and
Sph-I/II (Davidson et al.,
1988). The similarity of the wild-type sequence straddling the M4
mutation [5'-AAATTCCAC-3' (complementary strand:
5'-GTGGAATTT-3')] with that of GT-IIC
(5'-GTGGAATGT-3') suggests that Tead proteins recognize this
sequence. The signal of the Tead2-DNA complex was weaker than that of the
Tead4-DNA complex (Fig. 4A),
probably reflecting the weaker DNA-binding activity of Tead2 as reported
previously (Kaneko and DePamphilis,
1998
).
|
Expression of Tead in gastrulating mouse embryos
To understand which of the four mouse Tead family members is responsible
for activation of Foxa2, we studied the expression of these genes
between E6.5 and 9.0 by in situ hybridization. At E6.5, Tead2 was
expressed in the entire epiblast and mesoderm, but not in the extraembryonic
ectoderm or visceral endoderm (Fig.
5B,C). Tead3 and Tead4 were expressed throughout
the embryo in all germ layers, but with stronger expression in the
extraembryonic region and proximal portion of the embryo than in the distal
portion (Fig. 5D,E). Yap65, a
co-factor of Tead, was expressed throughout the embryo. Expression of
Tead1 was not observed in the embryonic portion at this stage, either
by in situ hybridization or RT-PCR (Fig.
5A and data not shown). At E7.5 and 8.5, in situ hybridization on
both whole-mount and sections showed wide expression of all four Tead
genes and Yap65 (Fig.
5G-K and data not shown), except for the extraembryonic visceral
endoderm at E7.5 and the heart at E8.5, where Tead2 was not
expressed. The Tead2 signal in the node and notochord was weaker
compared with the surrounding tissues, but clearly stronger than
non-expressing tissues (Fig.
5I,K). The expression of the other Tead genes was
essentially uniform at these stages (data not shown). Thus, all Tead
and Yap genes are expressed widely in the mouse embryo between E6.5
and 8.5, including the expression domain of Foxa2, suggesting that
all of them may be involved in the activation of the Foxa2
enhancer.
|
Activation of the CE in Wnt/ß-catenin-treated P19 cells could be the result of upregulation of Tead activity. To test this possibility, we used a reporter containing eight copies of a Tead-binding site, GT-IIC. This reporter was not activated by ß-catenin treatment of P19 cells, suggesting that ß-catenin treatment does not affect the activity of Tead (Fig. 6C). Therefore, the expression and/or activity of the other transcription factor acting on the 5' side of CE is regulated in P19 cells in response to this stimulus. Considering the wide expression of Tead in embryos, this other factor is likely to play an important role in the activation of the CE in the node. We refer to this unidentified transcription factor as `Partner Of Tead' (POT).
The activator function of Tead is required for notochord development and NE activation in vivo
To directly access the role of Tead in regulating enhancer activity, we
inhibited Tead activator function by locally expressing a repressor-modified
Tead (Tead-EnR: a fusion protein of the DNA-binding domain of Tead2 and the
repression domain of Drosophila Engrailed) in enhancer-LacZ
transgenic mouse embryos by electroporation. When a control (empty) plasmid
was electroporated into the distal tip of LHF stage embryos (the location of
the node), the notochord and endoderm cells efficiently incorporated the
plasmid at E8.5, as revealed by the activity of a co-electroporated marker,
membrane-tethered alkaline phosphatase
(Fig. 7A). The notochord cells
of these control embryos expressed both ß-galactosidase and alkaline
phosphatase (Fig. 7B). However,
when the Tead-EnR expression plasmid was electroporated into the same site,
ß-galactosidase expression in the midline was significantly reduced
(Fig. 7C). Eventual recovery of
ß-galactosidase expression in the posterior notochord may reflect the
fact that notochord progenitors in the ventral node are replenished from the
anterior primitive streak, as suggested by cell lineage analyses
(Cambray and Wilson, 2002;
Robb and Tam, 2004
).
Consistent with this notion, at 4 hours after electroporation, electroporated
cells were observed in the notochord and the anterior portion of the node, but
not in the posterior portion of the node (data not shown). In
Tead-EnR-expressed embryos, most of the notochord cells were absent,
suggesting that inhibition of Tead activator function disturbed proper
notochord development as well as expression of the enhancer transgene
(Fig. 7D; see Table S1 in the
supplementary material). These results suggest that Tead activity at the
Foxa2 NE enhancer is necessary for expression of endogenous
Foxa2, which is essential for notochord development.
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Discussion |
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Tead and POT cooperatively activate Foxa2 expression in the node
We showed that Tead and the unidentified transcription factor POT
cooperatively activate the CE, and that this is the key mechanism of enhancer
activation. Inhibition of Tead activity by Tead-EnR resulted in failure of
notochord formation. This is consistent with the idea that the NE enhancer is
the major driver of Foxa2 expression in the node/notochord, and that
Foxa2 is essential for node/notochord development
(Ang and Rossant, 1994;
Weinstein et al., 1994
).
Evolutionary conservation of the Tead-binding site among the node/notochord
enhancers of Foxa2 in mouse, chicken and fish
(Nishizaki et al., 2001
) and
mis-expression of foxa2 in Tead manipulated zebrafish embryos suggest
that Foxa2 regulation by Tead is evolutionarily conserved and thus a
fundamental mechanism. Whether or not POT is also involved in Foxa2
expression in other species is a question best addressed following the
molecular identification of POT.
The widespread expression of Tead and Yap suggests that spatially
restricted activation of the CE is achieved by localized expression of POT.
The most probable mechanism of CE activation is the induction of POT by Wnt
expressed in the primitive streak. A number of transcription factors expressed
in the node and primitive streak and/or induced by Wnt signaling in these
tissues, e.g. Sp5, Cdx, Brachyury, and Evx
(Dush and Martin, 1992;
Ikeya and Takada, 2001
;
Yamaguchi et al., 1999
),
failed to activate CE in P19 cells or to bind to the CE in vitro (data not
shown), suggesting that POT is likely to be a novel transcription factor
acting in the node and primitive streak downstream of Wnt signaling.
A model of Foxa2 enhancer activation in the node and the notochord
The NE enhancer of Foxa2 drives gene expression in both the node
and the notochord while CE drives expression only in the node, suggesting that
distinct mechanisms operate in these tissues. To summarize our results, we
would like to propose a model of Foxa2 enhancer activation in the
node and the notochord (Fig.
7E). In the node, Wnt signaling promotes binding of Tead and POT
to the CE, where they cooperatively activate the enhancer. Once the cells exit
from the node to form the notochord, the CE is not sufficient to drive gene
expression, probably because of the absence of POT. Tead may continue to bind
to the CE and may cooperate with other transcription factors that bind outside
the CE to activate the NE enhancer. Although we could not experimentally
address the question of whether Tead activates the enhancer only in the node
or in both the node and notochord, we prefer the latter idea, because Tead is
expressed in both tissues.
One interesting observation is that, although the CE drives gene expression
only in the node, disruption of CE (either the Tead site or POT site) in the
enhancer resulted in a loss of gene expression in both the node and notochord.
This raised the suggestion of a possible link between enhancer activation in
the notochord and its preceding activation in the node. If this is the case,
activation of CE by the Tead-POT complex in the node may lead to altered
chromatin structure and the recruitment of other transcription factors to the
enhancer. In the notochord, these transcription factors and Tead would then
cooperatively continue the activation. A similar two-step system of regulation
was recently determined for left-side-specific expression of the
Pitx2 enhancer, which is transiently activated by nodal-stimulated
FAST1 followed by maintenance by the widely expressed Nkx2
(Shiratori et al., 2001).
Verification of this two-step model for NE enhancer regulation awaits future
analysis.
Evolutionarily conserved function of Tead in gene regulation
In Drosophila, the Tead protein Scalloped (Sd) forms a complex
with its co-activator protein Vestigial (Vg) to regulate wing development
(Halder et al., 1998;
Simmonds et al., 1998
). The
Sd-Vg complex and other transcription factors cooperatively achieve
wing-field-specific gene expression. For example, the Sd-Vg complex cooperates
with Su(H) or Mad/Med to achieve Notch- or Dpp-signaling-regulated gene
expression in the wing field, but none of these transcription factors drives
gene expression by themselves in vivo
(Guss et al., 2001
). This is
reminiscent of the role of Tead in Foxa2 enhancer activation in mouse
embryos. A multimer of the CE, which contains the binding sites of Tead and
POT, efficiently activated gene expression in the node and primitive streak,
but a multimer of Tead-binding sites (GT-IIC)
(Davidson et al., 1988
) alone
did not produce reporter gene expression in transgenic mouse embryos (H.S.,
R.N. and H.S. unpublished). These observations suggest that these widely
expressed Tead transcription factors play crucial roles to achieve
spatiotemporally regulated gene expression by promoting the activity of other
transcription factors acting downstream of specific morphogenetic signals.
Considering the functional conservation of Tead between mouse and fly, it is
of interest to know if any of the four mouse homologs of fly Vg
(Chen et al., 2004
;
Maeda et al., 2002
;
Vaudin et al., 1999
) are
involved in the regulation of Foxa2 enhancer and Tead function in
mouse development.
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Conclusion |
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ACKNOWLEDGMENTS |
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Footnotes |
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Supplementary material for this article is available at http://dev.biologists.org/cgi/content/full/132/21/4719/DC1
* Present address: Department of Cellular Differentiation, Institute for
Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Ang, S. L. and Rossant, J. (1994). HNF-3 ß is essential for node and notochord formation in mouse development. Cell 78,561 -574.[CrossRef][Medline]
Beddington, R. S. (1994). Induction of a second
neural axis by the mouse node. Development
120,613
-620.
Bouillet, P., Oulad-Abdelghani, M., Ward, S. J., Bronner, S., Chambon, P. and Dolle, P. (1996). A new mouse member of the Wnt gene family, mWnt-8, is expressed during early embryogenesis and is ectopically induced by retinoic acid. Mech. Dev. 58,141 -152.[CrossRef][Medline]
Cambray, N. and Wilson, V. (2002). Axial progenitors with extensive potency are localised to the mouse chordoneural hinge. Development 129,4855 -4866.[Medline]
Chen, H. H., Mullett, S. J. and Stewart, A. F.
(2004). Vgl-4, a novel member of the vestigial-like family of
transcription cofactors, regulates alpha1-adrenergic activation of gene
expression in cardiac myocytes. J. Biol. Chem.
279,30800
-30806.
Chen, Z., Friedrich, G. A. and Soriano, P. (1994). Transcriptional enhancer factor 1 disruption by a retroviral gene trap leads to heart defects and embryonic lethality in mice. Genes Dev. 8,2293 -2301.[Abstract]
Davidson, B. P. and Tam, P. P. (2000). The node of the mouse embryo. Curr. Biol. 10,R617 -R619.[CrossRef][Medline]
Davidson, B. P., Kinder, S. J., Steiner, K., Schoenwolf, G. C. and Tam, P. P. (1999). Impact of node ablation on the morphogenesis of the body axis and the lateral asymmetry of the mouse embryo during early organogenesis. Dev. Biol. 211, 11-26.[CrossRef][Medline]
Davidson, B. P., Tsang, T. E., Khoo, P. L., Gad, J. M. and Tam, P. P. (2003). Introduction of cell markers into germ layer tissues of the mouse gastrula by whole embryo electroporation. Genesis 35,57 -62.[CrossRef][Medline]
Davidson, I., Xiao, J. H., Rosales, R., Staub, A. and Chambon, P. (1988). The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell 54,931 -942.[CrossRef][Medline]
De Robertis, E. M., Larrain, J., Oelgeschlager, M. and Wessely, O. (2000). The establishment of Spemann's organizer and patterning of the vertebrate embryo. Nat. Rev. Genet. 1, 171-181.[CrossRef][Medline]
Downs, K. M. and Davies, T. (1993). Staging of
gastrulating mouse embryos by morphological landmarks in the dissecting
microscope. Development
118,1255
-1266.
Dush, M. K. and Martin, G. R. (1992). Analysis of mouse Evx genes: Evx-1 displays graded expression in the primitive streak. Dev. Biol. 151,273 -287.[CrossRef][Medline]
Fujita, T., Nolan, G. P., Ghosh, S. and Baltimore, D. (1992). Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B. Genes Dev. 6, 775-787.[Abstract]
Gupta, M., Kogut, P., Davis, F. J., Belaguli, N. S., Schwartz,
R. J. and Gupta, M. P. (2001). Physical interaction
between the MADS box of serum response factor and the TEA/ATTS DNA-binding
domain of transcription enhancer factor-1. J. Biol.
Chem. 276,10413
-10422.
Gupta, M. P., Amin, C. S., Gupta, M., Hay, N. and Zak, R. (1997). Transcription enhancer factor 1 interacts with a basic helix-loop-helix zipper protein, Max, for positive regulation of cardiac alpha-myosin heavy-chain gene expression. Mol. Cell. Biol. 17,3924 -3936.[Abstract]
Guss, K. A., Nelson, C. E., Hudson, A., Kraus, M. E. and
Carroll, S. B. (2001). Control of a genetic regulatory
network by a selector gene. Science
292,1164
-1167.
Halder, G., Polaczyk, P., Kraus, M. E., Hudson, A., Kim, J.,
Laughon, A. and Carroll, S. (1998). The Vestigial and
Scalloped proteins act together to directly regulate wing-specific gene
expression in Drosophila. Genes Dev.
12,3900
-3909.
Henrique, D., Adam, J., Myat, A., Chitnis, A., Lewis, J. and Ish-Horowicz, D. (1995). Expression of a Delta homologue in prospective neurons in the chick. Nature 375,787 -790.[CrossRef][Medline]
Hibi, M., Hirano, T. and Dawid, I. B. (2002). Organizer formation and function. Res. Probl. Cell Diff. 40,48 -71.
Hogan, B., Beddington, R., Constantini, F. and Lacy, E. (1994). Manipulating the Mouse Embryo: Laboratory Manual, 2nd edn. New York: Cold Spring Harbor Laboratory Press.
Ikeya, M. and Takada, S. (2001). Wnt-3a is required for somite specification along the anteroposterior axis of the mouse embryo and for regulation of cdx-1 expression. Mech. Dev. 103,27 -33.[CrossRef][Medline]
Itasaki, N., Sharpe, J., Morrison, A. and Krumlauf, R. (1996). Reprogramming Hox expression in the vertebrate hindbrain: influence of paraxial mesoderm and rhombomere transposition. Neuron 16,487 -500.[CrossRef][Medline]
Jacquemin, P., Sapin, V., Alsat, E., Evain-Brion, D., Dolle, P. and Davidson, I. (1998). Differential expression of the TEF family of transcription factors in the murine placenta and during differentiation of primary human trophoblasts in vitro. Dev. Dyn. 212,423 -436.[CrossRef][Medline]
Jiang, S. W., Desai, D., Khan, S. and Eberhardt, N. L. (2000). Cooperative binding of TEF-1 to repeated GGAATG-related consensus elements with restricted spatial separation and orientation. DNA Cell Biol. 19,507 -514.[CrossRef][Medline]
Jiang, S. W., Dong, M., Trujillo, M. A., Miller, L. J. and
Eberhardt, N. L. (2001). DNA binding of TEA/ATTS domain
factors is regulated by protein kinase C phosphorylation in human
choriocarcinoma cells. J. Biol. Chem.
276,23464
-23470.
Joubin, K. and Stern, C. D. (1999). Molecular interactions continuously define the organizer during the cell movements of gastrulation. Cell 98,559 -571.[CrossRef][Medline]
Kamachi, Y., Uchikawa, M. and Kondoh, H. (2000). Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet. 16,182 -187.[CrossRef][Medline]
Kaneko, K. J. and DePamphilis, M. L. (1998). Regulation of gene expression at the beginning of mammalian development and the TEAD family of transcription factors. Dev. Genet. 22, 43-55.[CrossRef][Medline]
Kaneko, K. J., Cullinan, E. B., Latham, K. E. and DePamphilis,
M. L. (1997). Transcription factor mTEAD-2 is selectively
expressed at the beginning of zygotic gene expression in the mouse.
Development 124,1963
-1973.
Kinder, S. J., Tsang, T. E., Wakamiya, M., Sasaki, H., Behringer, R. R., Nagy, A. and Tam, P. P. (2001). The organizer of the mouse gastrula is composed of a dynamic population of progenitor cells for the axial mesoderm. Development 128,3623 -3634.[Medline]
Kispert, A., Vainio, S., Shen, L., Rowitch, D. H. and McMahon,
A. P. (1996). Proteoglycans are required for maintenance of
Wnt-11 expression in the ureter tips. Development
122,3627
-3637.
Klingensmith, J., Ang, S. L., Bachiller, D. and Rossant, J. (1999). Neural induction and patterning in the mouse in the absence of the node and its derivatives. Dev. Biol. 216,535 -549.[CrossRef][Medline]
Koshida, S., Shinya, M., Mizuno, T., Kuroiwa, A. and Takeda,
H. (1998). Initial anteroposterior pattern of the zebrafish
central nervous system is determined by differential competence of the
epiblast. Development
125,1957
-1966.
Kubo, F., Takeichi, M. and Nakagawa, S. (2003).
Wnt2b controls retinal cell differentiation at the ciliary marginal zone.
Development 130,587
-598.
Li, Q. and Verma, I. M. (2002). NF-kappaB regulation in the immune system. Nat. Rev. Immunol. 2, 725-734.[CrossRef][Medline]
Maeda, T., Chapman, D. L. and Stewart, A. F.
(2002). Mammalian vestigial-like 2, a cofactor of TEF-1
and MEF2 transcription factors that promotes skeletal muscle differentiation.
J. Biol. Chem. 277,48889
-48898.
Makita, R., Mizuno, T., Koshida, S., Kuroiwa, A. and Takeda, H. (1998). Zebrafish wnt11: pattern and regulation of the expression by the yolk cell and No tail activity. Mech. Dev. 71,165 -176.[CrossRef][Medline]
Maretto, S., Cordenonsi, M., Dupont, S., Braghetta, P.,
Broccoli, V., Hassan, A. B., Volpin, D., Bressan, G. M. and Piccolo,
S. (2003). Mapping Wnt/beta-catenin signaling during mouse
development and in colorectal tumors. Proc. Natl. Acad. Sci.
USA 100,3299
-3304.
Merrill, B. J., Pasolli, H. A., Polak, L., Rendl, M.,
Garcia-Garcia, M. J., Anderson, K. V. and Fuchs, E.
(2004). Tcf3: a transcriptional regulator of axis induction in
the early embryo. Development
131,263
-274.
Milewski, R. C., Chi, N. C., Li, J., Brown, C., Lu, M. M. and
Epstein, J. A. (2004). Identification of minimal enhancer
elements sufficient for Pax3 expression in neural crest and implication of
Tead2 as a regulator of Pax3. Development
131,829
-837.
Moon, R. T. and Kimelman, D. (1998). From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. BioEssays 20,536 -545.[CrossRef][Medline]
Niehrs, C. (2004). Regionally specific induction by the Spemann-Mangold organizer. Nat. Rev. Genet. 5,425 -434.[Medline]
Nikaido, M., Tada, M., Saji, T. and Ueno, N. (1997). Conservation of BMP signaling in zebrafish mesoderm patterning. Mech. Dev. 61, 75-88.[CrossRef][Medline]
Nishizaki, Y., Shimazu, K., Kondoh, H. and Sasaki, H. (2001). Identification of essential sequence motifs in the node/notochord enhancer of Foxa2 (Hnf3ß) gene that are conserved across vertebrate species. Mech. Dev. 102, 57-66.[CrossRef][Medline]
Petropoulos, H. and Skerjanc, I. S. (2002).
Beta-catenin is essential and sufficient for skeletal myogenesis in P19 cells.
J. Biol. Chem. 277,15393
-15399.
Robb, L. and Tam, P. P. (2004). Gastrula organiser and embryonic patterning in the mouse. Semin. Cell Dev. Biol. 15,543 -554.[CrossRef][Medline]
Sasaki, H. and Hogan, B. L. (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. and Hogan, B. L. (1994). HNF-3ß as a regulator of floor plate development. Cell 76,103 -115.[CrossRef][Medline]
Sasaki, H. and Hogan, B. L. (1996). Enhancer
analysis of the mouse HNF-3ß gene: regulatory elements for node/notochord
and floor plate are independent and consist of multiple sub-elements.
Genes Cells 1,59
-72.
Sasaki, H., Hui, C., Nakafuku, M. and Kondoh, H.
(1997). A binding site for Gli proteins is essential for
HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh
in vitro. Development
124,1313
-1322.
Sasaki, H., Nishizaki, Y., Hui, C., Nakafuku, M. and Kondoh,
H. (1999). Regulation of Gli2 and Gli3 activities by an
amino-terminal repression domain: implication of Gli2 and Gli3 as primary
mediators of Shh signaling. Development
126,3915
-3924.
Shiratori, H., Sakuma, R., Watanabe, M., Hashiguchi, H., Mochida, K., Sakai, Y., Nishino, J., Saijoh, Y., Whitman, M. and Hamada, H. (2001). Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2. Mol. Cell 7,137 -149.[CrossRef][Medline]
Simmonds, A. J., Liu, X., Soanes, K. H., Krause, H. M., Irvine,
K. D. and Bell, J. B. (1998). Molecular interactions
between Vestigial and Scalloped promote wing formation in Drosophila.
Genes Dev. 12,3815
-3820.
Stewart, A. F., Larkin, S. B., Farrance, I. K., Mar, J. H.,
Hall, D. E. and Ordahl, C. P. (1994). Muscle-enriched
TEF-1 isoforms bind M-CAT elements from muscle-specific promoters and
differentially activate transcription. J. Biol. Chem.
269,3147
-3150.
Sturm, K. and Tam, P. P. (1993). Isolation and culture of whole postimplantation embryos and germ layer derivatives. Methods Enzymol. 225,164 -190.[Medline]
Sugimoto, H., Bakovic, M., Yamashita, S. and Vance, D. E.
(2001). Identification of transcriptional enhancer factor-4 as a
transcriptional modulator of CTP:phosphocholine cytidylyltransferase alpha.
J. Biol. Chem. 276,12338
-12344.
Takada, S., Stark, K. L., Shea, M. J., Vassileva, G., McMahon, J. A. and McMahon, A. P. (1994). Wnt-3a regulates somite and tailbud formation in the mouse embryo. Genes Dev. 8,174 -189.[Abstract]
Takahashi, N., Ishihara, S., Takada, S., Tsukita, S. and Nagafuchi, A. (2000). Posttranscriptional regulation of alpha-catenin expression is required for Wnt signaling in L cells. Biochem. Biophys. Res. Commun. 277,691 -698.[CrossRef][Medline]
Tam, P. P. and Behringer, R. R. (1997). Mouse gastrulation: the formation of a mammalian body plan. Mech. Dev. 68,3 -25.[CrossRef][Medline]
Tam, P. P. and Steiner, K. A. (1999). Anterior
patterning by synergistic activity of the early gastrula organizer and the
anterior germ layer tissues of the mouse embryo.
Development 126,5171
-5179.
Tam, P. P. L. and Gad, J. M. (2004). Gastrulation in the mouse embryo. In Gastrulation: From cells to embryo (ed. C. D. Stern). New York: Cold Spring Harbor Laboratory Press.
Tam, P. P., Steiner, K. A., Zhou, S. X. and Quinlan, G. A. (1997). Lineage and functional analyses of the mouse organizer. Cold Spring Harb. Symp. Quant. Biol. 62,135 -144.[Medline]
Tang, K., Yang, J., Gao, X., Wang, C., Liu, L., Kitani, H., Atsumi, T. and Jing, N. (2002). Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells. Biochem. Biophys. Res. Commun. 293,167 -173.[CrossRef][Medline]
Tao, Q., Yokota, C., Puck, H., Kofron, M., Birsoy, B., Yan, D., Asashima, M., Wylie, C. C., Lin, X. and Heasman, J. (2005). Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell 120,857 -871.[CrossRef][Medline]
Thompson, M., Andrade, V. A., Andrade, S. J., Pusl, T., Ortega, J. M., Goes, A. M. and Leite, M. F. (2003). Inhibition of the TEF/TEAD transcription factor activity by nuclear calcium and distinct kinase pathways. Biochem. Biophys. Res. Commun. 301,267 -274.[CrossRef][Medline]
Ueda, Y., Hijikata, M., Takagi, S., Takada, R., Takada, S., Chiba, T. and Shimotohno, K. (2002). Wnt/beta-catenin signaling suppresses apoptosis in low serum medium and induces morphologic change in rodent fibroblasts. Int. J. Cancer 99,681 -688.[CrossRef][Medline]
Vassilev, A., Kaneko, K. J., Shu, H., Zhao, Y. and DePamphilis,
M. L. (2001). TEAD/TEF transcription factors utilize the
activation domain of YAP65, a Src/Yes-associated protein localized in the
cytoplasm. Genes Dev.
15,1229
-1241.
Vaudin, P., Delanoue, R., Davidson, I., Silber, J. and Zider,
A. (1999). TONDU (TDU), a novel human protein related to the
product of vestigial (vg) gene of Drosophila melanogaster interacts with
vertebrate TEF factors and substitutes for Vg function in wing formation.
Development 126,4807
-4816.
Weinstein, D. C., Ruiz i Altaba, A., Chen, W. S., Hoodless, P., Prezioso, V. R., Jessell, T. M. and Darnell, J. E., Jr (1994). The winged-helix transcription factor HNF-3 ß is required for notochord development in the mouse embryo. Cell 78,575 -588.[CrossRef][Medline]
Wilkinson, D. G. (1992). Whole mount in situ hybridization of vertebrate embryos. In In Situ Hybridization: A Practical Approach (ed. D. G. Wilkinson), pp.75 -84. Oxford: IRL Press.
Xiao, J. H., Davidson, I., Matthes, H., Garnier, J. M. and Chambon, P. (1991). Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1. Cell 65,551 -568.[CrossRef][Medline]
Yamaguchi, T. P., Takada, S., Yoshikawa, Y., Wu, N. and McMahon,
A. P. (1999). T (Brachyury) is a direct target of Wnt3a
during paraxial mesoderm specification. Genes Dev.
13,3185
-3190.
Yasunami, M., Suzuki, K. and Ohkubo, H. (1996). A novel family of TEA domain-containing transcription factors with distinct spatiotemporal expression patterns. Biochem. Biophys. Res. Commun. 228,365 -370.[CrossRef][Medline]
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