Brinker (Brk), a novel protein with features of a transcriptional repressor, regulates the graded response to Decapentaplegic (Dpp) in appendage primordia of Drosophila. Here, we show that in the embryo brk also has differential effects on Dpp target genes, depending on the level of Dpp activity required for their activation. Low-level target genes, like dpp itself, tolloid and early zerknullt, show strong ectopic expression in ventrolateral regions of brk mutant embryos; intermediate-level target genes like pannier show weak ectopic expression, while high-level target genes like u-shaped and rhomboid are not affected. Ectopic target gene activation in the absence of brk is independent of Dpp, Tkv and Medea, indicating that Dpp signaling normally antagonizes brk's repression of these target genes. brk is expressed like short gastrulation (sog) in ventrolateral regions of the embryo abutting the dpp domain. Here, both brk and sog antagonize the antineurogenic activity of Dpp so that only in brk sog double mutants is the neuroectoderm completely deleted.

Reference

Alberga
A.
,
Boulay
J. L.
,
Kempe
E.
,
Dennefeld
C.
,
Haenlin
M.
(
1991
)
The snail gene required for mesoderm formation in Drosophila is expressed dynamically in derivatives of all three germ layers.
Development
111
,
983
992
Anderson
K. V.
,
Bokla
L.
,
Nusslein-Volhard
C.
(
1985
)
Establishment of dorsal-ventral polarity in the Drosophila embryo the induction of polarity by the Toll gene product.
Cell
42
,
791
798
Biehs
B.
,
Francois
V.
,
Bier
E.
(
1996
)
The Drosophila short gastrulation gene prevents Dpp from autoactivating and suppressing neurogenesis in the neuroectoderm.
Genes Dev
10
,
2922
2934
Bier
E.
,
Jan
L. Y.
,
Jan
Y. N.
(
1990
)
rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster.
Genes Dev
4
,
190
203
Brummel
T. J.
,
Twombly
V.
,
Marques
G.
,
Wrana
J. L.
,
Newfeld
S. J.
,
Attisano
L.
,
Massague
J.
,
O'Connor
M. B.
,
Gelbart
W. M.
(
1994
)
Characterization and relationship of Dpp receptors encoded by the saxophone and thick veins genes in Drosophila.
Cell
78
,
251
261
Cabrera
C. V.
,
Martinez Arias
A.
,
Bate
M.
(
1987
)
The expression of three members of the achaete-scute gene complex correlates with neuroblast segregation in Drosophila.
Cell
50
,
425
434
Campbell
G.
,
Tomlinson
A.
(
1999
)
Transducing the Dpp morphogen gradient in the wing of Drosophila: Regulation of Dpp targets by brinker.
Cell
96
,
553
562
Cho
K. W. Y.
,
Blitz
I. L.
(
1998
)
BMPs, Smads and metalloproteases: extracellular and intracellular models of negative regulation.
Curr. Opin. Genet. Dev
8
,
443
449
Chou
T. B.
,
Perrimon
N.
(
1996
)
The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster.
Genetics
144
,
1673
1679
Cubadda
Y.
,
Heitzler
P.
,
Ray
R. P.
,
Bourouis
M.
,
Ramain
P.
,
Gelbart
W.
,
Simpson
P.
,
Haenlin
M.
(
1997
)
U-shaped encodes a zinc finger protein that regulates the proneural genes achaete and scute during the formation of bristles in Drosophila.
Genes Dev
11
,
3083
3095
D'Alessio
M.
,
Frasch
M.
(
1996
)
Msh may play a conserved role in dorsoventral patterning of the neuroectoderm and mesoderm.
Mech. Dev
58
,
217
231
Das
P.
,
Maduzia
L. L.
,
Wang
H.
,
Finelli
A. L.
,
Cho
S. H.
,
Smith
M. M.
,
Padgett
R. W.
(
1998
)
The Drosophila gene Medea demonstrates the requirement for different classes of Smads in Dpp signaling.
Development
125
,
1519
1528
Derynck
R.
,
Zhang
Y.
,
Feng
X. H.
(
1998
)
Smads: transcriptional activators of TGF-responses.
Cell
95
,
737
740
Ferguson
E. L.
(
1996
)
Conservation of dorsal-ventral patterning in arthropods and chordates.
Curr. Opin. Genet. Dev
6
,
424
431
Ferguson
E. L.
,
Anderson
K. V.
(
1992
)
Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo.
Cell
71
,
451
461
Ferguson
E. L.
,
Anderson
K. V.
(
1992
)
Localized enhancement and repression of the activity of the TGF-family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo.
Development
114
,
583
597
François
V.
,
Solloway
M.
,
O'Neill
J. W.
,
Emery
J.
,
Bier
E.
(
1994
)
Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene.
Genes Dev
8
,
2602
2616
Frasch
M.
(
1995
)
Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo.
Nature
374
,
464
467
Gaul
U.
,
Seifert
E.
,
Schuh
R.
,
Jaeckle
H.
(
1987
)
Analysis of Kruppel protein distribution during early Drosophila development reveals posttranscriptional regulation.
Cell
50
,
639
648
Golembo
M.
,
Yarnitzky
T.
,
Volk
T.
,
Shilo
B.-Z.
(
1999
)
Vein expression is induced by the EGF receptor pathway to provide a positive feedback loop in patterning the Drosophila embryonic ventral ectoderm.
Genes Dev
13
,
158
162
Haenlin
M.
,
McDonald
W. F.
,
Cibert
C.
,
Mohier
E.
(
1995
)
The angle of the dorsoventral axis with respect to the anteroposterior axis in the Drosophila embryo is controlled by the distribution of gurken mRNA in the oocyte.
Mech. Dev
49
,
97
106
Haerry
T. E.
,
Khalsa
O.
,
O'Connor
M. B.
,
Wharton
K. A.
(
1998
)
Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila.
Development
125
,
3977
3987
Heitzler
P.
,
Haenlin
M.
,
Ramain
P.
,
Calleja
M.
,
Simpson
P.
(
1996
)
A genetic analysis of pannier, a gene necessary for viability of dorsal tissues and bristle positioning in Drosophila.
Genetics
143
,
1271
1286
Heldin
C. H.
,
Miyazono
K.
,
Peter Ten
D.
(
1997
)
TGF- b signalling from cell membrane to nucleus through SMAD proteins.
Nature
390
,
465
471
Holley
S. A.
,
Jackson
P. D.
,
Sasai
Y.
,
Lu
B.
,
De Robertis
E. M.
,
Hoffmann
F. M.
,
Ferguson
E. L.
(
1995
)
A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin.
Nature
376
,
249
253
Holley
S. A.
,
Neul
J. L.
,
Attisano
L.
,
Wrana
J. L.
,
Sasai
Y.
,
O'Connor
M. B.
,
De Robertis
E. M.
,
Ferguson
E. L.
(
1996
)
The Xenopus dorsalizing factor noggin ventralizes Drosophila embryos by preventing DPP from activating its receptor.
Cell
86
,
607
617
Hoodless
P. A.
,
Haerry
T.
,
Abdollah
S.
,
Stapleton
M.
,
O'Connor
M. B.
,
Attisano
L.
,
Wrana
J. L.
(
1996
)
MADR1, a MAD-related protein that functions in BMP2 signaling pathways.
Cell
85
,
489
500
Hudson
J. B.
,
Podos
S. D.
,
Keith
K.
,
Simpson
S. L.
,
Ferguson
E. L.
(
1998
)
The DrosophilaMedea gene is required downstream of dpp and encodes a functional homolog of human Smad4.
Development
125
,
1407
1420
Ip
Y. T.
,
Park
R. E.
,
Kosman
D.
,
Bier
E.
,
Levine
M.
(
1992
)
The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo.
Genes Dev
6
,
1728
1739
Jaz'win'ska
A.
,
Kirov
N.
,
Wieschaus
E.
,
Roth
S.
,
Rushlow
C.
(
1999
)
The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation.
Cell
96
,
563
573
Khalsa
O.
,
Yoon
J. W.
,
Torres-Schumann
S.
,
Wharton
K. A.
(
1998
)
TGF-/BMP superfamily members, Gbb-60A and Dpp, cooperate to provide pattern information and establish cell identity in the Drosophila wing.
Development
125
,
2723
2734
Knust
E.
,
Schrons
H.
,
Grawe
F.
,
Campos Ortega
J. A.
(
1992
)
Seven genes of the enhancer of split complex of Drosophilamelanogaster encode helix-loop-helix proteins.
Genetics
132
,
505
518
Lecuit
T.
,
Brook
W. J.
,
Ng
M.
,
Calleja
M.
,
Sun
H.
,
Cohen
S. M.
(
1996
)
Two distinct mechanisms for long-range patterning by decapentaplegic in the Drosophila wing.
Nature
381
,
387
393
Lecuit
T.
,
Cohen
S. M.
(
1998
)
Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginal disc.
Development
125
,
4901
4907
Marques
G.
,
Musacchio
M.
,
Shimell
M. J.
,
Wunnenberg Stapleton
K.
,
Cho
K. W. Y.
,
O'Connor
M. B.
(
1997
)
Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins.
Cell
91
,
417
426
Minami
M.
,
Kinoshita
N.
,
Kamoshida
Y.
,
Tanimotot
H.
,
Tabata
T.
(
1999
)
brinker is a target of Dpp in Drosophila t that negatively regulates Dpp-depndent genes.
Nature
398
,
242
246
Nellen
D.
,
Affolter
M.
,
Basler
K.
(
1994
)
Receptor serine-threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic.
Cell
78
,
225
237
Nellen
D.
,
Burke
R.
,
Struhl
G.
,
Basler
K.
(
1996
)
Direct and long-range action of a DPP morphogen gradient.
Cell
85
,
357
368
Neul
J. L.
,
Ferguson
E. L.
(
1998
)
Spatially restricted activation of the SAX receptor by SCW modulates DPP/TKV signaling in Drosophila dorsal-ventral patterning.
Cell
95
,
483
494
Nguyen
M.
,
Park
S.
,
Marques
G.
,
Arora
K.
(
1998
)
Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors, SAX and TKV.
Cell
95
,
495
506
Noselli
S.
(
1998
)
JNK signalling and morphogenesis in Drosophila.
Trends Genet
14
,
33
38
O'Neill
J. W.
,
Bier
E.
(
1994
)
Double-label in situ hybridization using biotin and digoxigenin-tagged RNA probes.
Biotechniques
17
,
874
875
Patterson
G. I.
,
Koweek
A.
,
Wong
A.
,
Liu
Y.
,
Ruvkun
G.
(
1997
)
The DAF-3 Smad protein antagonizes TGF--related receptor signaling in the Caenorhabditis elegans dauer pathway.
Genes Dev
11
,
2679
2690
Penton
A.
,
Chen
Y.
,
Staehling-Hampton
K.
,
Wrana
J. L.
,
Attisano
L.
,
Szidonya
J.
,
Cassill
J. A.
,
Massague
J.
,
Hoffmann
F. M.
(
1994
)
Identification of two Bone Morphogenetic Protein type I receptors in Drosophila and evidence that Brk25D is a Decapentaplegic receptor.
Cell
78
,
239
250
Piccolo
S.
,
Agius
E.
,
Lu
B.
,
Goodman
S.
,
Dale
L.
,
De Robertis
E. M.
(
1997
)
Cleavage of chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity.
Cell
91
,
407
416
Ray
R. P.
,
Arora
K.
,
Nusslein Volhard
C.
,
Gelbart
W. M.
(
1991
)
The control of cell fate along the dorsal ventral axis of the Drosophila embryo.
Development
113
,
35
54
Roth
S.
,
Stein
D.
,
Nusslein-Volhard
C.
(
1989
)
A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo.
Cell
59
,
1189
1202
Rupp
R. A. W.
,
Snider
L.
,
Weintraub
H.
(
1994
)
Xenopus embryos regulate the nuclear localization of XMyoD.
Genes Dev
8
,
1311
1323
Rusch
J.
,
Levine
M.
(
1996
)
Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo.
Curr. Opin. Gen. Dev
6
,
416
423
Rushlow
C.
,
Frasch
M.
,
Doyle
H.
,
Levine
M.
(
1987
)
Maternal regulation of zerknullt a homoeobox gene controlling differentiation of dorsal tissues in Drosophila.
Nature
330
,
583
586
Sasai
Y.
,
Lu
B.
,
Steinbeisser
H.
,
Geissert
D.
,
Gont
L. K.
,
De Robertis
E. M.
(
1994
)
Xenopus chordin: A novel dorsalizing factor activated by organizer-specific homeobox genes.
Cell
79
,
779
790
Schmidt
J.
,
Francois
V.
,
Bier
E.
,
Kimelman
D.
(
1995
)
Drosophila short gastrulation induces an ectopic axis in Xenopus: Evidence for conserved mechanisms of dorsal-ventral patterning.
Development
121
,
4319
4328
Schweitzer
R.
,
Shaharabany
M.
,
Seger
R.
,
Shilo
B. Z.
(
1995
)
Secreted Spitz triggers the DER signaling pathway and is a limiting components in embryonic ventral ectoderm determination.
Genes Dev
9
,
1518
1529
Shimell
M. J.
,
Ferguson
E. L.
,
Childs
S. R.
,
Oconnor
M. B.
(
1991
)
The Drosophila dorsal-ventral patterning gene tolloid is related to human Bone Morphogenetic Protein 1.
Cell
67
,
469
482
Suzuki
A.
,
Chang
C.
,
Yingling
J. M.
,
Wang
X. F.
,
Hemmati Brivanlou
A.
(
1997
)
Smad5 induces ventral fates in Xenopus embryo.
Dev. Biol
184
,
402
405
Tautz
D.
,
Pfeifle
C.
(
1989
)
A non-radioactive in situ hybridization method for the localization of specific RNA in Drosophila embryos reveals translational control of the segmentation gene hunchback.
Chromosoma
98
,
81
85
Terracol
R.
,
Lengyel
J. A.
(
1994
)
The thick veins gene of Drosophila is required for dorsoventral polarity of the embryo.
Genetics
138
,
165
178
Thatcher
J. D.
,
Haun
C.
,
Okkema
P. G.
(
1999
)
The DAF-3 Smad binds DNA and represses gene expression in the Caenorhabditis elegans pharynx.
Development
126
,
97
107
Vincent
S.
,
Ruberte
E.
,
Grieder
N. C.
,
Chen
C. K.
,
Haerry
T.
,
Schuh
R.
,
Affolter
M.
(
1997
)
DPP controls tracheal cell migration along the dorsoventral body axis of the Drosophila embryo.
Development
124
,
2741
2750
Wappner
P.
,
Gabay
L.
,
Shilo
B. Z.
(
1997
)
Interactions between the EGF receptor and DPP pathways establish distinct cell fates in the tracheal placodes.
Development
124
,
4707
4716
Wharton
K. A.
,
Ray
R. P.
,
Gelbart
W. M.
(
1993
)
An activity gradient of Decapentaplegic is necessary for the specification of dorsal pattern elements in the Drosophila embryo.
Development
117
,
807
822
Whitman
M.
(
1998
)
Smads and early developmental signaling by the TGFsuperfamily.
Genes Dev
12
,
2445
2462
Wilson
P. A.
,
Lagna
G.
,
Suzuki
A.
,
Hemmati Brivanlou
A.
(
1997
)
Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1.
Development
124
,
3177
3184
Winick
J.
,
Abel
T.
,
Leonard
M. W.
,
Michelson
A. M.
,
Chardon-Loriaux
I.
,
Holmgren
R. A.
,
Maniatis
T.
,
Engel
J. D.
(
1993
)
A GATA family transcription factor is expressed along the embryonic dorsoventral axis in Drosophilamelanogaster.
Development
119
,
1055
1065
Wisotzkey
R. G.
,
Mehra
A.
,
Sutherland
D. J.
,
Dobens
L. L.
,
Liu
X.
,
Dohrmann
C.
,
Attisano
L.
,
Raftery
L. A.
(
1998
)
Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses.
Development
125
,
1433
1445
Zusman
S. B.
,
Sweeton
D.
,
Wieschaus
E. F.
(
1988
)
short gastrulation a mutation causing delays in stage-specific cell shape changes during gastrulation in Drosophila melanogaster.
Dev. Biol
129
,
417
427
This content is only available via PDF.