Little is known about the signal transduction pathways by which cells respond to mammalian TGF-beta s or to decapentaplegic (dpp), a Drosophila TGF-beta-related factor. Here we describe the genetic and molecular characterization of Drosophila schnurri (shn), a putative transcription factor implicated in dpp signaling. The shn protein has eight zinc fingers and is related to a human transcription factor, PRDII/MBPI/HIV-EP1, that binds to nuclear factor-kappa B-binding sites and activates transcription from the HIV long terminal repeat (LTR). shn mRNA is expressed in a dynamic pattern in the embryo that includes most of the known target tissues of dpp, including the dorsal blastoderm, the mesodermal germlayer and parasegments 4 and 7 of the midgut. Mutations in shn affect several developmental processes regulated by dpp including induction of visceral mesoderm cell fate, dorsal/ventral patterning of the lateral ectoderm and wing vein formation. Absence of shn function blocks the expanded expression of the homeodomain protein bagpipe in the embryonic mesoderm caused by ectopic dpp expression, illustrating a requirement for shn function downstream of dpp action. We conclude that shn function is critical for cells to respond properly to dpp and propose that shn protein is the first identified downstream component of the signal transduction pathway used by dpp and its receptors.

Reference

Arora
K.
,
Levine
M. S.
,
O'Connor
M. B.
(
1994
)
The screw gene encodes a ubiquitously expressed member of the TGF-family required for specification of dorsal cell fates in the Drosophila embryo.
Genes Dev
8
,
2588
2601
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
Azpiazu
N.
,
Frasch
M.
(
1993
)
tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila.
Genes Dev
7
,
1325
1340
Baldwin
A. S.
Jr.
,
LeClair
K. P.
,
Singh
H.
,
Sharp
P. A.
(
1990
)
A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatability complex and kappa immunoglobulin genes.
Mol. Cell. Biol
10
,
1406
1414
Basler
K.
,
Struhl
G.
(
1994
)
Hedgehog, a product of posterior compartment cells in Drosophila, organizes anterior compartment pattern.
Nature
368
,
208
214
Bienz
M.
(
1994
)
Homeotic genes and positional signaling in Drosophila viscera.
Trends in Genet
10
,
22
26
Bodmer
R.
(
1993
)
The gene tinman is required for specification of the heart and visceral muscles in Drosophila.
Development
118
,
719
729
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
Bryant
P. J.
(
1988
)
Localized cell death caused by mutations in a Drosophila gene coding for a transforming growth factor-homolog.
Dev. Biol
128
,
386
395
Carroll
S. B.
,
Scott
M. P.
(
1985
)
Localization of the fushi tarazu protein during Drosophila embryogenesis.
Cell
43
,
47
57
Childs
S. R.
,
Wrana
J. L.
,
Arora
K.
,
Attisano
L.
,
O'Connor
M. B.
,
Massague
J.
(
1993
)
Identification of a Drosophila activin receptor.
Proc. Natl. Acad. Sci. USA
90
,
9475
9479
Churchill
M. E. A.
,
Sukuki
M.
(
1989
)
‘SPKK’ motifs prefer to bind DNA at A/T-rich sites.
EMBO J
8
,
4189
4195
Cohen
B.
,
Simcox
A. A.
,
Cohen
S. M.
(
1993
)
Allocation of the imaginal primordia in the Drosophila embryo.
Development
117
,
597
608
Doctor
J. S.
,
Jackson
P. D.
,
Rashka
K. E.
,
Visalli
M.
,
Hoffmann
F. M.
(
1992
)
Sequence, biochemical characterization, and developmental expression of a new member of the TGF-superfamily in Drosophila melanogaster.
Dev. Biol
151
,
491
505
Fan
C.-M.
,
Maniatis
T.
(
1990
)
A DNA-binding protein containing two widely separated zinc finger motifs that recognize the same DNA sequence.
Genes Dev
4
,
29
42
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
Frasch
M.
(
1995
)
Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo.
Nature
374
,
464
467
Heberlein
U.
,
Wolff
T.
,
Rubin
G. M.
(
1993
)
The TGFhomolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina.
Cell
75
,
913
926
Hill
C. S.
,
Packman
L. C.
,
Thomas
J. O.
(
1990
)
Phosphorylation at clustered-Ser-Pro-X-Lys/Arg-motifs in sperm specific histones H1 and H2B.
EMBO J
9
,
805
813
Hursh
D.A.
,
Padgett
R.W.
,
Gelbart
W.M.
(
1993
)
Cross regulation of decapentaplegic and Utrabithorax transcription in the embryonic visceral mesoderm of Drosophila.
Development
117
,
1211
1222
Immergluck
K.
,
Lawrence
P. A.
,
Bienz
M.
(
1990
)
Induction across germ layers in Drosophila mediated by a genetic cascade.
Cell
62
,
261
268
Ip
Y. T.
,
Reach
M.
,
Engstrom
Y.
,
Kadalayil
L.
,
Cai
H.
,
González-Crespo
S.
,
Tatei
K.
,
Levine
M.
(
1993
)
Dif, a dorsal -related gene that mediates an immune response in Drosophila.
Cell
75
,
753
763
Irish
V. I.
,
Gelbart
W. M.
(
1987
)
The decapentaplegic gene is required for dorsal-ventral patterning of the Drosophila embryo.
Genes Dev
1
,
868
879
Jackson
P. D.
,
Hoffmann
F. M.
(
1994
)
Embryonic expression patterns of the Drosophila decapentaplegic gene: Separate regulatory elements control blastoderm expression and lateral ectodermal expression.
Dev. Dynamics
199
,
28
44
Kingsley
D. M.
(
1994
)
The TGF-superfamily: new members, new receptors, and new genetic tests of function in different organisms.
Genes Dev
8
,
133
146
Klug
A.
,
Rhodes
D.
(
1987
)
‘Zinc fingers’: A novel protein motif for nucleic acid recognition.
Trends Biochem. Sci
12
,
464
469
Letsou
A.
,
Arora
K.
,
Wrana
J. L.
,
Simin
K.
,
Twombly
V.
,
Jamal
J.
,
Staehling-Hampton
K.
,
Hoffmann
F. M.
,
Gelbart
W. M.
,
Massague
J.
,
O'Connor
M. B.
(
1995
)
Drosophila dpp signaling is mediated by the punt gene product: a dual ligand type II receptor of the TGF-receptor family.
Cell
80
,
899
908
Maekawa
T.
,
Sakura
H.
,
Sudo
T.
,
Ishii
S.
(
1989
)
Putative metal structure of the human immunodeficiency virus type 1 enhancer binding protein HIV-EP1.
J. Biol. Chem
264
,
14591
14593
Mastick
G.S.
,
McKay
R.
,
Oligino
T.
,
Donovan
K.
,
Lopez
A.J.
(
1995
)
Identification of target genes regulated by homeotic proteins in Drosophila melanogaster through genetic selection of Ultrabithorax protein-binding sites in yeast.
Genetics
139
,
349
363
Masucci
J. D.
,
Miltenberger
R. J.
,
Hoffmann
F. M.
(
1990
)
Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3′ cis -regulatory elements.
Genes Dev
4
,
2011
2023
Mitchelmore
C.
,
Traboni
C.
,
Cortese
R.
(
1990
)
Isolation of two cDNAs encoding zinc finger proteins which bind to the1-antitrypsin promoter and to the major histocompatibility complex class I enhancer.
Nucleic Acids Research
19
,
141
147
Miyamoto
H.
,
Nihonmatsu
I.
,
Kondo
S.
,
Ueda
R.
,
Togashi
S.
,
Hirata
K.
,
Ikegami
Y.
,
Yamamoto
D.
(
1995
)
canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.
Genes Dev
9
,
612
625
Miyazono
K.
,
Ten Dijke
P.
,
Ichijo
H.
,
Heldin
C. H.
(
1994
)
Receptors for transforming growth factor-.
Adv. Immunology
55
,
181
220
Nakamura
T.
,
Donovan
D. M.
,
Hamada
K.
,
Sax
C. M.
,
Norman
B.
,
Flanagan
J. R.
,
Ozato
K.
,
Westphal
H.
,
Piatigorsky
J.
(
1990
)
Regulation of the mouseA-crystallin gene: Isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes.
Mol. Cell. Biol
10
,
3700
3708
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
Nomura
N.
,
Zhao
M.-J.
,
Nagase
T.
,
Maekawa
T.
,
Ishizaki
R.
,
Tabata
S.
,
Ishii
S.
(
1991
)
HIV-EP2, a new member of the gene family encoding the human immunodeficiency virus type I enhancer-binding protein.
J. Biol. Chem
266
,
8590
8594
Padgett
R. W.
,
St Johnston
R. D.
,
Gelbart
W. M.
(
1987
)
A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-family.
Nature
325
,
81
84
Panganiban
G. E. F.
,
Reuter
R.
,
Scott
M. P.
,
Hoffmann
F. M.
(
1990
)
A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis.
Development
110
,
1041
1050
Patel
N. H.
,
Snow
P. M.
,
Goodman
C. S.
(
1987
)
Characterization and cloning of fasciclin III: A glycoprotein expressed on a subset of neurons and axon pathways in Drosophila.
Cell
48
,
975
988
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
Raftery
L. A.
,
Twombly
V.
,
Wharton
K.
,
Gelbart
W. M.
(
1995
)
Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila.
Genetics
139
,
241
254
Ramain
P.
,
Heitzler
P.
,
Haenlin
M.
,
Simpson
P.
(
1993
)
pannier, a negative regulator of achaete and scute in Drosophila, encodes a zinc finger protein with homology to the vertebrate transcription factor GATA-1.
Development
119
,
1277
1291
Reuter
R.
,
Panganiban
G. E. F.
,
Hoffmann
F. M.
,
Scott
M. P.
(
1990
)
Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos.
Development
110
,
1031
1040
Ron
D.
,
Brasier
A. R. J. F.
,
Habener
J. F.
(
1991
)
Angiotensinogen gene-inducible enhancer-binding protein 1, a member of a new family of large nuclear proteins that recognize nuclear factorB-binding sites through a zinc finger motif.
Mol. Cell. Biol
11
,
2887
2895
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
Ruberte
E.
,
Marty
T.
,
Nellen
D.
,
Affolter
M.
,
Basler
K.
(
1995
)
An absolute requirement for both the type II and type I receptors, punt and thickveins for dpp signaling in vivo.
Cell
80
,
889
897
Rushlow
C. A.
,
Han
K.
,
Manley
J. L.
,
Levine
M.
(
1989
)
The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila.
Cell
59
,
1165
1177
Rustgi
A. K.
,
Van ‘T Veer
L. J.
,
Bernards
R.
(
1990
)
Two genes encode factors with NF-B-and H2TF1-like DNA-binding properties.
Proc. Natl. Acad. Sci. USA
87
,
8707
8710
Seeler
J.-S.
,
Muchardt
C.
,
Suessle
A.
,
Gaynor
R. B.
(
1994
)
Transcription factor PRDII-BF1 activates human Immunodeficiency virus type 1 gene expression.
J. Virology
68
,
1002
1009
Sekelsky
J. J.
,
Newfeld
S. J.
,
Raftery
L. A.
,
Chartoff
E. H.
,
Gelbart
W. M.
(
1995
)
Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophilamelanogaster.
Genetics
139
,
1347
1358
Simon
M. A.
(
1994
)
Signal transduction during the development of the Drosophila R7 photoreceptor.
Dev. Biol
166
,
431
442
Spencer
F.A.
,
Hoffmann
F.M.
,
Gelbart
W.M.
(
1982
)
Decapentaplegic: A gene complex affecting morphogenesis in Drosophila melanogaster.
Cell
28
,
451
461
St Johnston
R. D.
,
Gelbart
W. M.
(
1987
)
decapentaplegic transcripts are localized along the dorsal-ventral axis of the Drosophila embryo.
EMBO J
6
,
2785
2791
Staehling-Hampton
K.
,
Hoffmann
F. M.
,
Baylies
M. K.
,
Rushton
E.
,
Bate
M.
(
1994
)
dpp induces mesodermal gene expression in Drosophila.
Nature
372
,
783
786
Staehling-Hampton
K.
,
Hoffmann
F. M.
(
1994
)
Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp and wingless, causing morphological defects.
Dev. Biol
164
,
502
512
Steward
R.
(
1989
)
Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function.
Cell
59
,
1179
1188
Suzuki
M.
(
1989
)
SPXX, a frequent sequence motif in gene regulatory proteins.
J. Mol. Biol
207
,
61
84
Thuringer
F.
,
Cohen
S.M.
,
Bienz
M.
(
1993
)
Dissection of an indirect autoregulatory response of a homeotic Drosophila gene.
EMBO J
12
,
2419
2430
Tremml
G.
,
Bienz
M.
(
1992
)
Induction of labial expression in the Drosophila endoderm: response elements for dpp signaling and for autoregulation.
Development
116
,
447
456
Van ‘T Veer
L. J.
,
Lutz
P. M.
,
Isselbacher
K. J.
,
Bernards
R.
(
1992
)
Structure and expression of major histocompatibility complex-binding protein 2, a 275-kDa zinc finger protein that binds to an enhancer of major histocompatability complex class I genes.
Proc. Natl. Acad. Sci. USA
89
,
8971
8975
Wharton
K. A.
,
Thomsen
G. H.
,
Gelbart
W. M.
(
1991
)
Drosophila 60A gene, a new TGF-family member is closely related to human bone morphogenetic proteins.
Proc. Natl. Acad. Sci. USA
88
,
9214
9218
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 Drosophila melanogaster.
Development
119
,
1055
1065
Wrana
J. L.
,
Attisano
L.
,
Cárcamo
J.
,
Zentella
A.
,
Doody
J.
,
Laiho
M.
,
Wang
X.-F.
,
Massague
J.
(
1992
)
TGFsignals through a heteromeric protein kinase receptor complex.
Cell
71
,
1003
1014
Wrana
J. L.
,
Tran
H.
,
Attisano
L.
,
Arora
K.
,
Childs
S. R.
,
Massague
J.
,
O'Connor
M. B.
(
1994
)
Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster form an activin receptor complex.
Mol. Cell Biol
14
,
944
950
Wu
L.-C.
,
Mak
C.-H.
,
Dear
N.
,
Boehm
T.
,
Foroni
L.
,
Rabbitts
T. H.
(
1993
)
Molecular cloning of a zinc finger protein which binds to the heptamer of the signal sequence for V(D)J recombination.
Nucleic Acids Res
21
,
5067
5073
Xie
T.
,
Finelli
A. L.
,
Padgett
R. W.
(
1994
)
The Drosophilasaxophone gene: A serine-threonine kinase receptor of the TGF-superfamily.
Science
263
,
1756
1759
This content is only available via PDF.