Members of the steroid/thyroid hormone receptor superfamily are involved in the control of cell identity and of pattern formation during embryonic development. Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) can act as regulators of various steroid/thyroid hormone receptor pathways. To begin to study the role of COUP-TFs during embryogenesis, we cloned a chicken COUP-TF (cCOUP-TF II) which is highly homologous to human COUP-TF II. Northern analysis revealed high levels of cCOUP-TF II transcripts during organogenesis. Nuclear extracts from whole embryos and from embryonic spinal cords were used in electrophoretic mobility shift assays. These assays showed that COUP-TF protein is present in these tissues and is capable of binding to a COUP element (a direct repeat of AGGTCA with one base pair spacing). Analysis of cCOUP-TF expression by in situ hybridization revealed high levels of cCOUP-TF II mRNA in the developing spinal motor neurons. Since the ventral properties of the spinal cord, including the development of motor neurons, is in part established by inductive signals from the notochord, we transplanted an additional notochord next to the dorsal region of the neural tube in order to induce ectopic motor neurons. We observed that an ectopic notochord induced cCOUP-TF II gene expression in the dorsal spinal cord in a region coextensive with ectopic domains of SC1 and Islet-1, two previously identified motor neuron markers. Collectively, our studies raise the possibility that cCOUP-TF II is involved in motor neuron development.

Adan
R. A. H.
,
Cox
J. J.
,
Beischlag
T. V.
,
Burbach
J. P. H.
(
1993
)
Acomposite hormone response element mediates the transactivation of the rat oxytocin gene by different classes of nuclear hormone receptors.
Mol. Endocrinol
7
,
47
57
Adan
R. A.
,
Cox
J. J.
,
van Kats
J. P.
,
Burbach
J. P. H.
(
1992
)
Thyroid hormone regulates the oxytocin gene.
J. Biol. Chem
267
,
3771
3777
Beato
M.
(
1989
)
Gene regulation by steroid hormones.
Cell
56
,
335
344
Burbach
J. P. H.
,
Adan
R. A. H.
,
van Tol
H. H. M.
,
Verbeeck
M. A. E.
,
Axelson
J. F.
,
Van Leeuwen
F. W.
,
Beekman
J. M.
,
Ab
G.
(
1990
)
Regulation of the rat oxytocin gene by estradiol.
J. Neuroendocrinol
2
,
633
639
Chan
S.-M.
,
Xu
N.
,
Niemeyer
C. C.
,
Bone
J. R.
,
Flytzanis
C. N.
(
1992
)
SpCOUP-TF: A sea urchin member of the steroid/thyroid hormone receptor family.
Proc. Natl. Acad. Sci. USA
89
,
10568
10572
Cooney
A. J.
,
Leng
X.
,
Tsai
S. Y.
,
O'Malley
B. W.
,
Tsai
M.-J.
(
1993
)
Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoid acid receptors.
J. Biol. Chem
268
,
4152
4160
Cooney
A. J.
,
Tsai
S. Y.
,
O'Malley
B. W.
,
Tsai
M.-J.
(
1992
)
Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors.
Mol. Cell. Biol
12
,
4153
4163
de The
H.
,
Vivanco-Ruiz
M. d. M.
,
Tiollais
P.
,
Stunnenberg
H.
,
Dejean
A.
(
1990
)
Identification of a retinoic acid responsive element in the retinoic acidreceptor gene.
Nature
343
,
177
180
Durand
B.
,
Saunders
M.
,
Leroy
P.
,
Leid
M.
,
Chambon
P.
(
1992
)
All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs.
Cell
71
,
73
85
Ericson
J.
,
Thor
S.
,
Edlund
T.
,
Jessell
T. M.
,
Yamada
T.
(
1992
)
Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1.
Science
256
,
1555
1560
Evans
R. M.
(
1988
)
The steroid and thyroid hormone receptor superfamily.
Science
240
,
889
895
Figdor
M. C.
,
Stern
C. D.
(
1993
)
Segmental organization of embryonic diencephalon.
Nature
363
,
630
634
Fjose
A.
,
Nornes
S.
,
Weber
U.
,
Mlodzik
M.
(
1993
)
Functional conservation of vertebrate seven-up related genes in neurogenesis and eye development.
EMBO J
12
,
1403
1414
Gossett
L. A.
,
Kelvin
D. J.
,
Sternberg
E. A.
,
Olson
E. N.
(
1989
)
A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes.
Mol. Cell. Biol
9
,
5022
5033
Goulding
M. D.
,
Lumsden
A.
,
Gruss
P.
(
1993
)
Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord.
Development
117
,
1001
1016
Graham
A.
,
Maden
M.
,
Krumlauf
R.
(
1991
)
The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development.
Development
112
,
255
264
Green
S.
,
Chambon
P.
(
1988
)
Nuclear receptors enhance our understanding of transcription regulation.
Trends Genet
4
,
309
314
Gruss
P.
,
Walther
C.
(
1992
)
Pax in development.
Cell
69
,
719
722
Hamada
K.
,
Gleason
S. L.
,
Levi
B.-Z.
,
Hirschfeld
S.
,
Appella
E.
,
Ozato
K.
(
1989
)
H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.
Proc. Natl. Acad. Sci.USA
86
,
8289
8293
Hamburger
V.
,
Hamilton
H. L.
(
1951
)
A series of normal stages in the development of the chick embryo.
J. Morph
88
,
49
92
Hirano
S.
,
Fuse
S.
,
Sohal
G. S.
(
1991
)
The effect of the floor plate on pattern and polarity in the developing central nervous system.
Science
251
,
310
313
Hollyday
M.
,
Hamburger
V.
(
1977
)
An autoradiographic study of the formation of the lateral motor column in the chick embryo.
Brain Res
132
,
197
208
Karlsson
O.
,
Thor
S.
,
Norberg
T.
,
Ohlsson
H.
,
Edlund
T.
(
1990
)
Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo-and a Cys-His domain.
Nature
344
,
879
882
Kliewer
S. A.
,
Umesono
K.
,
Heyman
R. A.
,
Mangelsdorf
D. J.
,
Dyck
J. A.
,
Evans
R. M.
(
1992
)
Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling.
Proc. Natl. Acad. Sci. USA
89
,
1448
1452
Ladias
J. A. A.
,
Karathanasis
S. K.
(
1991
)
Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily.
Science
251
,
561
565
Leid
M.
,
Kastner
P.
,
Chambon
P.
(
1992
)
Multiplicity generates diversity in the retinoic acid signalling pathway.
Trends Biochem. Sci
17
,
427
433
Levi-Montalcini
R.
(
1950
)
The origin and development of the visceral system in the spinal cord of the chick embryo.
J. Morph
86
,
253
284
Linney
E.
(
1992
)
Retinoic acid receptors: Transcription factors modulating gene regulation, development, and differentiation.
Curr. Topics in Dev. Biol
27
,
309
350
Loring
J. F.
,
Barker
D. L.
,
Erickson
C. A.
(
1988
)
Migration and differentiation of neural crest and ventral neural tube cells in vitro: Implications for in vitro and in vivo studies of the neural crest.
J. Neurosci
8
,
1001
1015
Lunn
E. R.
,
Scourfield
J.
,
Keynes
R. J.
,
Stern
C. D.
(
1987
)
The neural tube origin of ventral root sheath cells in the chick embryo.
Development
101
,
247
254
Maden
M.
,
Ong
D. E.
,
Chytil
F.
(
1990
)
Retinoid binding protein distribution in the developing mammalian nervous system.
Development
109
,
75
80
Mangelsdorf
D. J.
,
Borgmeyer
U.
,
Heyman
R. A.
,
Zhou
J. Y.
,
Ong
E. S.
,
Oro
A. E.
,
Kakizuka
A.
,
Evans
R. M.
(
1992
)
Characterization of three RXR genes that mediate the action of 9- cis retinoic acid.
Genes Dev
6
,
329
344
Matharu
P. J.
,
Sweeney
G. E.
(
1992
)
Cloning and sequencing of a COUP transcription factor gene expressed in Xenopus embryos.
Biochim. Biophys. Acta
1129
,
331
334
McGinnis
W.
,
Krumlauf
R.
(
1992
)
Homeobox genes and axial patterning.
Cell
68
,
283
302
Miyajima
N.
,
Kadowaki
Y.
,
Fukushige
S.
,
Shimizu
S.
,
Semba
K.
,
Yamanashi
Y.
,
Matsubara
K.
,
Toyoshima
K.
,
Yamamoto
T.
(
1988
)
Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other.
Nucl. Acids Res
16
,
11057
11074
Mlodzik
M.
,
Hiromi
Y.
,
Weber
U.
,
Goodman
C. S.
,
Rubin
G. M.
(
1990
)
The Drosophilaseven-up gene, a member of the steroid receptor gene superfamily, controls photoreceptor cell fates.
Cell
60
,
211
224
Muto
K.
,
Noji
S.
,
Nohno
T.
,
Koyama
E.
,
Myokai
F.
,
Nishijima
K.
,
Saito
T.
,
Taniguchi
S.
(
1991
)
Involvement of retinoic acid and its receptorin differentiation of motoneurons in chick spinal cord.
Neurosci. Letters
129
,
39
42
Oro
A. E.
,
McKeown
M.
,
Evans
R. M.
(
1992
)
The Drosophila nuclear receptors: new insight into the actions of nuclear receptors in development.
Curr. Opin. Gen. Develop
2
,
269
274
Petkovich
M.
(
1992
)
Regulation of gene expression by vitamin A: the role of nuclear retinoic acid receptors.
Annu. Rev. Nutr
12
,
443
471
Prasad
A.
,
Hollyday
M.
(
1991
)
Development and migration of avian sympathetic preganglionic neurons.
J. Comp. Neurol
307
,
237
258
Richard
S.
,
Zingg
H. H.
(
1990
)
The human oxytocin gene promoter is regulated by estrogens.
J. Biol. Chem
265
,
6098
6103
Richard
S.
,
Zingg
H. H.
(
1991
)
Identification of a retinoic acid response element in the human oxytocin promoter.
J. Biol. Chem
266
,
21428
21433
Richie
H. H.
,
Wang
L.-H.
,
Tsai
S.
,
O'Malley
B. W.
,
Tsai
M.-J.
(
1990
)
COUP-TF gene: a structure unique for the steroid/thyroid receptor superfamily.
Nucl. Acids Res
18
,
6857
6862
Ruberte
E.
,
Friederich
V.
,
Chambon
P.
,
Morriss-Kay
G.
(
1993
)
Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development.
Development
118
,
267
282
Sagami
I.
,
Tsai
S. Y.
,
Wang
H.
,
Tsai
M.-J.
,
O'Malley
B. W.
(
1986
)
Identification of two factors required for transcription of the ovalbumin gene.
Mol. Cell. Biol
6
,
4259
4267
Segars
J. H.
,
Marks
M. S.
,
Hirschfeld
S.
,
Driggers
P. H.
,
Martinez
E.
,
Grippo
J. F.
,
Wahli
W.
,
Ozato
K.
(
1993
)
Inhibition of estrogen-responsive gene activation by the retinoid X receptor: evidence for multiple inhibitory pathways.
Mol. Cell. Biol
13
,
2258
2268
Smith
D. B.
,
Johnson
K. S.
(
1988
)
Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
Gene
67
,
31
40
Smith
S. M.
,
Eichele
G.
(
1991
)
Temporal and regional differences in the expression pattern of distinct retinoic acid receptor- transcripts in the chick embryo.
Development
111
,
245
252
Smith
W. C.
,
Nakshatri
H.
,
Leroy
P.
,
Rees
J.
,
Chambon
P.
(
1991
)
A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter.
EMBO J
10
,
2223
2230
Strähle
U.
,
Klock
G.
,
Schutz
G.
(
1987
)
A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression.
Proc. Natl. Acad. Sci. USA
84
,
7871
7875
Sucov
H. M.
,
Murakami
K. K.
,
Evans
R. M.
(
1990
)
Characterization of an autoregulated response element in the mouse retinoic acid receptor type gene.
Proc. Natl. Acad. Sci.USA
87
,
5392
5396
Tanaka
H.
,
Matsui
T.
,
Agata
A.
,
Tomura
M.
,
Kubota
I.
,
McFarland
K. C.
,
Kohr
B.
,
Lee
A.
,
Phillips
H. S.
,
Shelton
D. L.
(
1991
)
Molecular cloning and expression of a novel adhesion molecule, SC1.
Neuron
7
,
535
545
Tanaka
H.
,
Obata
K.
(
1984
)
Developmental changes in unique cell surface antigens of chick embryo spinal motoneurons and ganglion cells.
Dev. Biol
106
,
26
37
Tran
P.
,
Zhang
X.-K.
,
Salbert
G.
,
Hermann
T.
,
Lehmann
J. M.
,
Pfahl
M.
(
1992
)
COUP orphan receptors are negative regulators of retinoic acid response pathways.
Mol. Cell. Biol
12
,
4666
4676
Tugwood
J. D.
,
Issemann
I.
,
Anderson
R. G.
,
Bundell
K. R.
,
McPheat
W. L.
,
Green
S.
(
1992
)
The mouse peroxisome proliferator activated receptor recognizes a response element in the 5flanking sequence of the rat acyl CoA oxidase gene.
EMBO J
11
,
433
439
van Straaten
H. M. W.
,
Thors
F.
,
Wiertz-Hoessels
E. L.
,
Hekking
J. W. M.
,
Drukker
J.
(
1985
)
Effect of a notochordal implant on the early morphogenesis of the neural tube and neuroblasts: histometrical and histological results.
Dev. Biol
110
,
247
254
Wang
L.-H.
,
Ing
N. H.
,
Tsai
S. Y.
,
O'Malley
B. W.
,
Tsai
M.-J.
(
1991
)
The COUP-TFs compose a family of functionally related transcription factors.
Gene Express
1
,
207
216
Wang
L.-H.
,
Tsai
S. Y.
,
Cook
R. G.
,
Beattie
W. G.
,
Tsai
M.-J.
,
O'Malley
B. W.
(
1989
)
COUP transcription factor is a member of the steroid receptor superfamily.
Nature
340
,
163
166
Wehrenberg
U.
,
Ivell
R.
,
Walther
N.
(
1992
)
The COUP transcription factor (COUP-TF) is directly involved in the regulation of oxytocin gene expression in luteinizing bovine granulosa cells.
Biochem. Biophys. Res. Comm
189
,
496
503
Widom
R. L.
,
Rhee
M.
,
Karathanasis
S. K.
(
1992
)
Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXRand retinoic acid.
Mol. Cell. Biol
12
,
3380
3389
Yamada
T.
,
Pfaff
S. L.
,
Edlund
T.
,
Jessell
T. M.
(
1993
)
Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate.
Cell
73
,
673
686
Yamada
T.
,
Placzek
M.
,
Tanaka
H.
,
Dodd
J.
,
Jessell
T. M.
(
1991
)
Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord.
Cell
64
,
635
647
This content is only available via PDF.