Delta and Notch are required for partitioning of vein and intervein cell fates within the provein during Drosophila metamorphosis. We find that partitioning of these fates is dependent on Delta-mediated signalling from 22 to 30 hours after puparium formation at 25 degrees C. Within the provein, Delta is expressed more highly in central provein cells (presumptive vein cells) and Notch is expressed more highly in lateral provein cells (presumptive intervein cells). Accumulation of Notch in presumptive intervein cells is dependent on Delta signalling activity in presumptive vein cells and constitutive Notch receptor activity represses Delta accumulation in presumptive vein cells. When Delta protein expression is elevated ectopically in presumptive intervein cells, complementary Delta and Notch expression patterns in provein cells are reversed, and vein loss occurs because central provein cells are unable to stably adopt the vein cell fate. Our findings imply that Delta-Notch signalling exerts feedback regulation on Delta and Notch expression during metamorphic wing vein development, and that the resultant asymmetries in Delta and Notch expression underlie the proper specification of vein and intervein cell fates within the provein.
REFERENCES
Artavanis-Tsakonas
S.
, Matsuno
K.
, Fortini
M. E.
(1995
) Notch signalling.
Science
268
, 225
–232
Brand
A. H.
, Perrimon
N.
(1993
) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
, 401
–415
de Celis
(1997
) Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing.
Development
124
, 1007
–1018
de Celis
J. F.
, García-Bellido
A.
(1994
) Modifications of the Notch function by Abruptex mutations in Drosophila melanogaster.
Genetics
136
, 183
–194
de Celis
J. F.
, García-Bellido
A.
(1994
) Roles of the Notch gene in Drosophila wing morphogenesis.
Mech. Dev
46
, 109
–122
Dexter
J. S.
(1914
) The analysis of a case of continuous variation in Drosophila by a study of its linkage relationships.
Am. Nat
68
, 712
–758
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.
, Johanson
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
Fehon
R. G.
, Kooh
P. J.
, Rebay
I.
, Regan
C. L.
, Xu
T.
, Muskavitch
M. A. T.
, Artavanis-Tsakonas
S.
(1990
) Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF homologous genes in Drosophila.
Cell
61
, 523
–534
Foster
G. G.
(1975
) Negative complementation at the Notch locus of Drosophila melanogaster.
Genetics
81
, 99
–120
Fristrom
D.
, Gotwals
P.
, Eaton
S.
, Kornberg
T. B.
, Sturtevant
M.
, Bier
E.
, Fristrom
J. W.
(1994
) blistered: a gene required for vein/intervein formation in wings of Drosophila.
Development
120
, 2661
–2671
Fristrom
D.
, Wilcox
M.
, Fristrom
J.
(1993
) The distribution of PS integrins, laminin A, and F-actin during key stages in Drosophila wing development.
Development
117
, 509
–523
Gallyas
F.
, Göres
T.
, Merchenthaler
I.
(1982
) High-grade intensification of the end-product of the diaminobenzidine reaction for peroxidase histochemistry.
J. Histochem. Cytochem
30
, 183
–184
García-Bellido
A.
, de Celis
J. F.
(1992
) Developmental genetics of the venation pattern of Drosophila.
Ann. Rev. Gen
26
, 277
–304
Gu
Y.
, Hukriede
N. A.
, Fleming
R. J.
(1995
) Serrate expression can functionally replace Delta activity during neuroblast segregation in the Drosophila embryo.
Development
121
, 855
–865
Heitzler
P.
, Simpson
P.
(1991
) The choice of cell fate in the epidermis of Drosophila.
Cell
64
, 1083
–1092
Heitzler
P.
, Simpson
P.
(1993
) Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions.
Development
117
, 1113
–1123
Henderson
S. T.
, Gao
D.
, Lambie
E. J.
, Kimble
J.
(1994
) lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans.
Development
120
, 2913
–2924
Hoppe
P. E.
, Greenspan
R. J.
(1986
) Local function of the Notch gene for embryonic ectodermal pathway choice in Drosophila.
Cell
46
, 773
–783
Hoppe
P. E.
, Greenspan
R. J.
(1990
) The Notch locus of Drosophila is required in epidermal cells for epidermal development.
Development
109
, 875
–885
Kooh
P. J.
, Fehon
R. G.
, Muskavitch
M. 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.
, Alton
A. K.
, Fechtel
K.
, Kooh
P. J.
, Muskavitch
M. A.
(1988
) Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factors of vertebrates.
Genes Dev
2
, 1723
–1735
Lambie
E.
, Kimble
J.
(1991
) Two homologous genes, lin-12 and glp-1, have overlapping functions.
Development
112
, 231
–240
Li
K.
, Kaufman
T. C.
(1996
) The Homeotic Target Gene centrosomin Encodes an Essential Centrosomal Component.
Cell
85
, 585
–596
Lieber
T.
, Kidd
S.
, Alcamo
E.
, Corbin
V.
, Young
M. W.
(1993
) Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei.
Genes Dev
7
, 1949
–1965
Liposits
Z. S.
, Setálo
G. Y.
, Lerko
B. F.
(1984
) Application of the silver-gold intensified 3,3-diaminobenzidine chromatin to the light and electron microscopic detection of the luteinizing hormone releasing hormone detection system of the rat brain.
Neuroscience
13
, 513
–525
Lyman
D. F.
, Yedvobnick
B.
(1995
) Drosophila Notch receptor activity suppresses Hairless function during adult external sensory organ development.
Genetics
141
, 1491
–1505
Micchelli
C. A.
, Rulifson
E. J.
, Blair
S. S.
(1997
) The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless, and a dominant negative role for Delta and Serrate.
Development
124
, 1485
–1495
Muskavitch
M. A. T.
(1994
) Delta-Notch signaling and Drosophila cell fate choice.
Dev. Biol
166
, 415
–430
Palka
J.
, Schubiger
M.
, Schwaninger
H.
(1990
) Neurogenic and antineurogenic effects from modifications at the Notch locus.
Development
109
, 167
–175
Parks
A. L.
, Turner
F. R.
, Muskavitch
M. A. T.
(1995
) Relationships between complex Delta expression and the specification of retinal cell fates during Drosophila eye development.
Mech. Dev
50
, 201
–216
Parody
T. R.
, Muskavitch
M. A. T.
(1993
) The pleiotropic function of Delta during postembryonic development of Drosophila melanogaster.
Genetics
135
, 527
–539
Portin
P.
(1975
) Allelic negative complementation at the Abruptex locus of Drosophila melanogaster.
Genetics
81
, 121
–133
Rebay
I.
, Fehon
R. G.
, Artavanis-Tsakonas
S.
(1993
) Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor.
Cell
74
, 319
–329
Rebay
I.
, Fleming
R. J.
, Fehon
R. G.
, Cherbas
L.
, Cherbas
P.
, Artavanis-Tsakonas
S.
(1991
) Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor.
Cell
67
, 687
–699
Seydoux
G.
, Greenwald
I.
(1989
) Cell autonomy of lin-12 function in a cell fate decision in C. elegans.
Cell
57
, 1237
–1245
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
Struhl
G.
, Fitzgerald
K.
, Greenwald
I.
(1993
) Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.
Cell
74
, 331
–345
Sturtevant
M. A.
, Bier
E.
(1995
) Analysis of the genetic hierarchy guiding wing vein development in Drosophila.
Development
121
, 785
–801
Sturtevant
M. A.
, O'Neill
J. W.
, Bier
E.
(1994
) Down-regulation of DrosophilaEgf-r mRNA levels following hyperactivated receptor signaling.
Development
120
, 2593
–2600
Tax
F.
, Yeagers
J. J.
, Thomas
J. H.
(1994
) Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila.
Nature
368
, 150
–154
Waddington
C. H.
(1940
) The genetic control of wing development in Drosophila.
J. Genetics
41
, 75
–139
Welshons
W.J.
(1965
) Analysis of a gene in Drosophila.
Science
150
, 1122
–1129
Wilkinson
H. A.
, Fitzgerald
K.
, Greenwald
I.
(1994
) Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to cell commitment in a C. elegans cell fate decision.
Cell
79
, 1187
–1198
Wilson
C.
, Pearson
R. K.
, Bellen
H. J.
, O'Kane
C. J.
, Grossniklaus
U.
, Gehring
W. J.
(1989
) P-element-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila.
Genes Dev
3
, 1301
–1313
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1997
