The veins in the Drosophila wing have a characteristic width, which is regulated by the activity of the Notch pathway. The expression of the Notch-ligand Delta is restricted to the developing veins, and coincides with places where Notch transcription is lower. We find that this asymmetrical distribution of ligand and receptor leads to activation of Notch on both sides of each vein within a territory of Delta-expressing cells, and to the establishment of boundary cells that separate the vein from adjacent interveins. In these cells, the expression of the Enhancer of split gene m beta is activated and the transcription of the vein-promoting gene veinlet is repressed, thus restricting vein differentiation. We propose that the establishment of vein thickness utilises a combination of mechanisms that include: (1) independent regulation of Notch and Delta expression in intervein and vein territories, (2) Notch activation by Delta in cells where Notch and Delta expression overlaps, (3) positive feedback on Notch transcription in cells where Notch has been activated and (4) repression of veinlet transcription by E(spl)m beta and maintenance of Delta expression by veinlet/torpedo activity.
REFERENCES
Artavanis-Tsakonas
S.
, Matsuno
K.
, Fortini
M. E.
(1995
) Notch Signalling.
Science
268
, 225
–232
Artavanis-Tsakonas
S.
, Simpson
P.
(1991
) Choosing a cell fate: a view from the Notch locus.
Trends Genet
7
, 403
–408
Baker
N.
, Mlodzik
M.
, Rubin
G. M.
(1990
) Spacing differentiation in the developing eye: a fibrinogen-related lateral inhibitor encoded by scabrous.
Science
250
, 1370
–1377
Bang
A. G.
, Posakony
J. W.
(1992
) The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development.
Genes Dev
6
, 1752
–1769
Bier
E.
, Jan
L. Y.
, Yan
Y. N.
(1990
) rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster.
Genes Dev
4
, 190
–203
Brand
A. H.
, Perrimon
N.
(1993
) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
, 401
–415
Brunner
D.
, Oellers
N.
, Szabad
J.
, Biggs
W. H.
, Zipursky
S. L.
, Hafen
E.
(1994
) A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signalling pathaways.
Cell
76
, 875
–888
Cubas
P.
, de Celis
J. F.
, Campuzano
S.
, Modolell
J.
(1991
) Proneural clusters of achaete-scute expression and the generation of sensory organs in the Drosophila imaginal wing disc.
Genes Dev
5
, 996
–1008
Davies
A. G.
, Game
A. Y.
, Chen
Z.
, Williams
T. J.
, Goodall
S.
, Yen
J. L.
, McKenzie
J. A.
, Batterham
P.
(1996
) Scalloped wings is the Lucilia cuprina Notch homologue and a candidate for the Modifier of fitness and asymmetry of Diazinon resistance.
Genetics
143
, 1321
–1337
de Celis
J. F.
, Garcia-Bellido
A.
(1994
) Roles of the Notch gene in Drosophila wing morphogenesis.
Mech. Dev
46
, 109
–122
de Celis
J. F.
, Llimargas
M.
, Casanova
J.
(1995
) ventral veinless, the gene encoding the Cf1a transcription factor, links positional information and cell differentiation during embryonic and imaginal development in Drosophila melanogaster.
Development
121
, 3405
–3416
de Celis
J. F.
, Baonza
A.
, Garcia-Bellido
A.
(1995
) Behavior of extramacrochaetae mutant cells during Drosophila wing morphogenesis.
Mech. Dev
53
, 209
–222
de Celis
J. F.
, de Celis
J.
, Ligoxiars
P.
, Preiss
A.
, Delidakis
C.
, Bray
S.
(1996
) Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development.
Development
122
, 2719
–2728
de Celis
J. F.
, Garcia-Bellido
A.
, Bray
S.
(1996
) Activation and function of Notch at the dorsoventral boundary in the Drosophila wing imaginal disc.
Development
122
, 359
–369
de la Concha
A.
, Dietrich
U.
, Weigel
D.
, Campos-Ortega
J. A.
(1988
) Functional interactions of neurogenic genes of Drosophila melanogaster.
Genetics
118
, 499
–508
Delidakis
C.
, Artavanis-Tsakonas
S.
(1992
) The Enhancer of split locus of Drosophila encodes seven independent helix-loop-helix proteins.
Proc. Nat. Acad. Sci. USA
89
, 8731
–8735
Diaz-Benjumea
F.
, Hafen
E.
(1994
) The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development.
Development
120
, 569
–578
Doherty
D.
, Feger
G.
, Younger-Shepherd
S.
, Jan
L. Y.
, Jan
Y. N.
(1996
) Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation.
Genes Dev
10
, 421
–434
Fehon
R. G.
, Johansen
K.
, Rebay
I.
, Artavanis-Tsakonas
S.
(1991
) Complex cellular and subcellular regulation of Notch expression during embryonic and imaginal development of Drosophila: implications for Notch function.
J. Cell Biol
113
, 657
–669
Fortini
M. E.
, Artavanis-Tsakonas
S.
(1994
) The Suppressor of Hairless protein participates in Notch receptor signaling.
Cell
79
, 273
–282
Fristrom
D.
, Wilcox
M.
, Fristron
J.
(1993
) The distribution of PS integrins, laminin A ad F-actin during key stages in Drosophila wing development.
Development
117
, 509
–523
Heberlein
U.
, Hariharan
I. K.
, Rubin
G. M.
(1993
) Star is required for neuronal differentiation in the Drosophila retina and displays dosage-sensitive interactions with Ras1.
Dev. Biol
160
, 51
–63
Horvitz
H. R.
, Sternberg
P. W.
(1991
) Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva.
Nature
351
, 535
–541
Jennings
B.
, Preiss
A.
, Delidakis
C.
, Bray
S.
(1994
) The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo.
Development
120
, 3537
–3548
Kelley
M. R.
, Kidd
S.
, Deutsh
W. A.
, Young
M. W.
(1987
) Mutations altering the structure of epidermal growth factor-like coding sequences at the Drosophila Notch locus.
Cell
51
, 539
–548
Kidd
S.
, Lockett
T. J.
, Young
M. W.
(1983
) The Notch locus of Drosophila melanogaster.
Cell
34
, 421
–433
Knust
E.
, Schrons
H.
, Grawe
F.
, Campos-Ortega
J. A.
(1992
) Seven genes of the Enhancer of split complex of Drosophila melanogaster encode Helix-loop-Helix protein.
Genetics
132
, 505
–518
Kooh
P. J.
, Fehon
R. G.
, Muskavitch
A. T.
(1993
) Implications of dynamic patterns of Delta and Notch expression for cellular interactions during Drosophila development.
Development
117
, 493
–507
Kopczynski
C. C. K. A. A.
, Fetchel
K.
, Kool
P. J.
, Muskavitch
A. T.
(1988
) Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates.
Genes Dev
2
, 1723
–1735
Lecourtois
M.
, Schweisguth
F.
(1995
) The neurogenic Suppressor of Hairless DNA-binding protein mediates the transcriptional activation of the Enhancer of split Complex genes triggered by Notch signalling.
Genes Development
9
, 2598
–2608
Montagne
J.
, Groppe
J.
, Guillemin
K.
, Krasnow
M. A.
, Gehring
W.
, Affolter
M.
(1996
) The Drosophila Serum Response Factor gene is required for the formation of intervein tissue of the wing and is allelic to blistered.
Development
122
, 2589
–2597
Noll
R.
, Sturtevant
M. A.
, Gollapudi
R. R.
, Bier
E.
(1994
) New functions of the Drosophila rhomboid gene during embryonic and adult development are revealed by a novel genetic method, enhancer piracy.
Development
120
, 2329
–2338
Parody
T. R.
, Muskavitch
M. A. T.
(1993
) The pleiotropic function of Delta during postembryonic development of Drosophila melanogaster.
Genetics
135
, 527
–539
Price
J. V.
, Clifford
R. J.
, Schupbach
T.
(1989
) The maternal ventralizing locus torpedo is allelic to faint little ball, an embryonic lethal, and encodes the Drosophila EGF receptor homolog.
Cell
56
, 1085
–1092
Schnepp
B.
, Grumbling
G.
, Donaldson
T.
, Simcox
A.
(1996
) Vein is a novel component in the Drosophila epidermal growth factor receptor pathway with similarity to the neuregulins.
Genes Dev
10
, 2302
–2313
Schrons
H.
, Knust
E.
, Campos-Ortega
J. A.
(1992
) The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells.
Genetics
132
, 481
–503
Schweisguth
F.
, Posakony
J. W.
(1992
) Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates.
Cell
69
, 1199
–1212
Schweisguth
F.
, Posakony
J. W.
(1994
) Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis.
Development
120
, 1433
–1441
Shellenbarger
D. L.
, Mohler
J. D.
(1978
) Temperature-sensitive periods and autonomy of pleiotropic effects of l(1)Nts1, a conditional Notch lethal in Drosophila.
Dev. Biol
62
, 432
–446
Simcox
A.
, Grumbling
G.
, Schnepp
B.
, Bennington-Mathias
C.
, Hersperger
E.
, Shearn
A.
(1996
) Molecular, phenotypic, and expression analysis of vein, a gene required for growth of the Drosophila wing disc.
Dev. Biol
177
, 475
–489
Sturtevant
M. A.
, Bier
E.
(1995
) Analysis of the genetic hierarchy guiding wing vein development in Drosophila.
Development
121
, 785
–801
Sturtevant
M. A.
, Roark
M.
, Bier
E.
(1993
) The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signalling pathway.
Genes Dev
7
, 961
–973
Sweeney
S.
, Broadie
K.
, Keane
J.
, Niemann
H.
, O'Kane
C.
(1995
) Targeted expression of Tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects.
Neuron
14
, 341
–351
Thomas
U.
, Jonsson
F.
, Speicher
S. A.
, Knust
E.
(1995
) Phenotypic and molecular characterization of SerD, a dominant allele of the Drosophila gene Serrate.
Genetics
139
, 203
–213
Vassin
H.
, Bremer
K. A.
, Knust
E.
, Campos-Ortega
J. A.
(1987
) The neurogenic gene Delta of Drosophila melanogaster is expressed in neurogenic territories and encodes a putative transmembrane protein with EGF-like repeats.
EMBO J
6
, 3431
–3440
Wilkinson
H. A.
, Fitzkerald
K.
, Greenwald
I.
(1994
) Reciprocal changes in expression of the receptor Lin-12 and its ligand Lag-2 prior to commitment in a C. elegans cell fate decision.
Cell
79
, 1187
–1198
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