Drosophila wings are patterned by a morphogen, Decapentaplegic (Dpp), a member of the TGFbeta superfamily, which is expressed along the anterior and posterior compartment boundary. The distribution and activity of Dpp signaling is controlled in part by the level of expression of its major type I receptor, thickveins (tkv). The level of tkv is dynamically regulated by En and Hh. We have identified a novel gene, master of thickveins (mtv), which downregulates expression of tkv in response to Hh and En. mtv expression is controlled by En and Hh, and is complementary to tkv expression. In this report, we demonstrate that mtv integrates the activities of En and Hh that shape tkv expression pattern. Thus, mtv plays a key part of regulatory mechanism that makes the activity gradient of the Dpp morphogen.

Reference

Alcedo
J.
,
Ayzenzon
M.
,
Von
O. T.
,
Noll
M.
,
Hooper
J. E.
(
1996
)
The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal.
Cell
86
,
221
232
Basler
K.
,
Struhl
G.
(
1994
)
Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.
Nature
368
,
208
214
Brand
A. H.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
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
Capdevila
J.
,
Estrada
M. P.
,
Sanchez
H. E.
,
Guerrero
I.
(
1994
)
The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.
EMBO J
13
,
71
82
Chen
Y.
,
Struhl
G.
(
1996
)
Dual roles for Patched in sequestering and transducing Hedgehog.
Cell
87
,
553
563
Chen
Y.
,
Struhl
G.
(
1998
)
In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex.
Development
125
,
4943
4948
de Celis
J. F.
,
Barrio
R.
,
Kafatos
F. C.
(
1996
)
A gene complex acting downstream of dpp in Drosophila wing morphogenesis.
Nature
381
,
421
424
de Celis
J. F.
,
Barrio
R.
(
2000
)
Function of the spalt/spalt-related gene complex in positioning the veins in the Drosophila wing.
Mech. Dev
91
,
31
41
Dyson
S.
,
Gurdon
J. B.
(
1998
)
The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors.
Cell
93
,
557
568
Garcia-Bellido
A.
,
Ripoll
P.
,
Morata
G.
(
1973
)
Developmental compartmentalization of the wing disk of Drosophila.
Nature
245
,
251
253
Grimm
S.
,
Pflugfelder
G. O.
(
1996
)
Control of the gene optomotor-blind in Drosophila wing development by decapentaplegic and wingless.
Science
271
,
1601
1604
Gurdon
J. B.
,
Dyson
S.
,
St Johnston
D.
(
1998
)
Cells' perception of position in a concentration gradient.
Cell
95
,
159
162
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
Ingham
P. W.
,
Taylor
A. M.
,
Nakano
Y.
(
1991
)
Role of the Drosophila patched gene in positional signalling.
Nature
353
,
184
187
Inoue
H.
,
Imamura
T.
,
Ishidou
Y.
,
Takase
M.
,
Udagawa
Y.
,
Oka
Y.
,
Tsuneizumi
K.
,
Tabata
T.
,
Miyazono
K.
,
Kawabata
M.
(
1998
)
Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp.
Mol. Biol. Cell
9
,
2145
2156
Ito
K.
,
Awano
W.
,
Suzuki
K.
,
Hiromi
Y.
,
Yamamoto
D.
(
1997
)
The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells.
Development
124
,
761
771
Jiang
J.
,
Struhl
G.
(
1995
)
Protein kinase A and Hedgehog signaling in Drosophila limb development.
Cell
80
,
563
572
Lawrence
P. A.
,
Struhl
G.
(
1996
)
Morphogens, compartments, and pattern:lessons from Drosophila?.
Cell
85
,
951
961
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
Lepage
T.
,
Cohen
S. M.
,
Diaz
B. F.
,
Parkhurst
S. M.
(
1995
)
Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning.
Nature
373
,
711
715
Li
W.
,
Ohlmeyer
J. T.
,
Lane
M. E.
,
Kalderon
D.
(
1995
)
Function of protein kinase A in Hedgehog signal transduction and Drosophila imaginal disc development.
Cell
80
,
553
562
Macias-Silva
M.
,
Abdollah
S.
,
Hoodless
P. A.
,
Pirone
R.
,
Attisano
L.
,
Wrana
J. L.
(
1996
)
MADR2 is a substrate of the TGF-receptor and its phosphorylation is required for nuclear accumulation and signaling.
Cell
87
,
1215
1224
Mullor
J. L.
,
Calleja
M.
,
Capdevila
J.
,
Guerrero
I.
(
1997
)
Hedgehog activity, independent of Decapentaplegic, participates in wing disc patterning.
Development
124
,
1227
1237
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
Neumann
C. J.
,
Cohen
S. M.
(
1997
)
Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing.
Development
124
,
871
880
Newfeld
S. J.
,
Mehra
A.
,
Singer
M. A.
,
Wrana
J. L.
,
Attisano
L.
,
Gelbart
W. M.
(
1997
)
Mothers against dpp participates in a DDP/TGF-responsive serine-threonine kinase signal transduction cascade.
Development
124
,
3167
3176
Pan
D.
,
Rubin
G. M.
(
1995
)
cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs.
Cell
80
,
543
552
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
Persson
U.
,
Izumi
H.
,
Souchelnytskyi
S.
,
Itoh
S.
,
Grimsby
S.
,
Engstrom
U.
,
Heldin
C.-H.
,
Funa
K.
,
ten Dijke
P.
(
1998
)
The L45 loop in type I receptors for TGF-family members is a critical determinant in specifying Smad isoform activation.
FEBS Lett
434
,
83
87
Rao
Y.
,
Pang
P.
,
Ruan
W.
,
Gunning
D.
,
Zipursky
S. L.
(
2000
)
brakeless is required for photoreceptor growth-cone targeting in Drosophila.
Proc. Natl. Acad. Sci. USA
97
,
5966
5971
Sanicola
M.
,
Sekelsky
J.
,
Elson
S.
,
Gelbart
W. M.
(
1995
)
Drawing a stripe in Drosophila imaginal disks: negative regulation of decapentaplegic and patched expression by engrailed.
Genetics
139
,
745
756
Senti
K.
,
Keleman
K.
,
Eisenhaber
F.
,
Dickson
B. J.
(
2000
)
brakeless is required for lamina targeting of R1-R6 axons in the Drosophila visual system.
Development
127
,
2291
2301
Shimizu
K.
,
Gurdon
J. B.
(
1999
)
A quantitative analysis of signal transduction from activin receptor to nucleus and its relevance to morphogen gradient interpretation.
Proc. Natl. Acad. Sci. USA
96
,
6791
6796
Singer
M. A.
,
Penton
A.
,
Twombly
V.
,
Hoffmann
F. M.
,
Gelbart
W. M.
(
1997
)
Signaling through both type I DPP receptors is required for anterior-posterior patterning of the entire Drosophila wing.
Development
124
,
79
89
Strigini
M.
,
Cohen
S. M.
(
1997
)
A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing.
Development
124
,
4697
4705
Sturtevant
M. A.
,
Biehs
B.
,
Marin
E.
,
Bier
E.
(
1997
)
The spalt gene links the A/P compartment boundary to a linear adult structure in the Drosophila wing.
Development
124
,
21
32
Tabata
T.
,
Kornberg
T. B.
(
1994
)
Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs.
Cell
76
,
89
102
Tabata
T.
,
Schwartz
C.
,
Gustavson
E.
,
Ali
Z.
,
Kornberg
T. B.
(
1995
)
Creating a Drosophila wing de novo, the role of engrailed, and the compartment border hypothesis.
Development
121
,
3359
3369
Tanimoto
H.
,
Itoh
S.
,
ten Dijke
P.
,
Tabata
T.
(
2000
)
Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs.
Mol. Cell
5
,
59
71
Tsuneizumi
K.
,
Nakayama
T.
,
Kamoshida
Y.
,
Kornberg
T. B.
,
Christian
J. L.
,
Tabata
T.
(
1997
)
Daughters against dpp modulates dpp organizing activity in Drosophila wing development.
Nature
389
,
627
631
van den Heuvel
M.
,
Ingham
P. W.
(
1996
)
smoothened encodes a receptor-like serpentine protein required for Hedgehog signalling.
Nature
382
,
547
551
Xie
T.
,
Finelli
A. L.
,
Padgett
R. W.
(
1994
)
The Drosophila saxophone gene: a serine-threonine kinase receptor of the TGF-superfamily.
Science
263
,
1756
1759
Xu
T.
,
Rubin
G. M.
(
1993
)
Analysis of genetic mosaics in developing and adult Drosophila tissues.
Development
117
,
1223
1237
Yang
P.
,
Shaver
S. A.
,
Hilliker
A. J.
,
Sokolowski
M. B.
(
2000
)
Abnormal turning behavior in Drosophila larvae. Identification and molecular analysis of scribbler (sbb).
Genetics
155
,
1161
1174
Zecca
M.
,
Basler
K.
,
Struhl
G.
(
1995
)
Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing.
Development
121
,
2265
2278
Zecca
M.
,
Basler
K.
,
Struhl
G.
(
1996
)
Direct and long-range action of a Wingless morphogen gradient.
Cell
87
,
833
844
This content is only available via PDF.