Signalling by the epidermal growth factor receptor (EGFR) plays a critical role in the segmental patterning of the ventral larval cuticle in Drosophila: by expressing a dominant-negative EGFR molecule or Spitz, an activating ligand of EGFR, we show that EGFR signalling specifies the anterior denticles in each segment of the larval abdomen. We provide evidence that these denticles derive from a segmental zone of embryonic cells in which EGFR signalling activity is maximal. Within each segment, there is a competition between the denticle fate specified by EGFR signalling and the naked cuticle fate specified by Wingless signalling. The final pattern of the denticle belts is the product of this antagonism between the two signalling pathways. Finally, we show that the segmental zones of high EGFR signalling activity depend on bithorax gene function and that they account for the main difference in shape between abdominal and thoracic denticle belts.

REFERENCES

REFERENCES
Baker
N.
(
1988
)
Embryonic and imaginal requirements for wg, a segment polarity gene.
Dev. Biol
125
,
96
108
Baker
N. E.
(
1987
)
Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos.
EMBO J
6
,
1765
1774
Bejsovec
A.
,
Martinez-Arias
A.
(
1991
)
Roles of wingless in patterning the larval epidermis of Drosophila.
Development
113
,
471
485
Bejsovec
A.
,
Wieschaus
E.
(
1993
)
Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos.
Development
119
,
501
517
Bienz
M.
(
1994
)
Homeotic genes and positional signalling in the Drosophila viscera.
Trends Genet
10
,
22
26
Bienz
M.
,
Tremml
G.
(
1988
)
Domain of Ultrabithorax expression in Drosophila visceral mesoderm from autoregulation and exclusion.
Nature
333
,
576
578
Bier
E.
,
Jan
L. Y.
,
Jan
Y. N.
(
1990
)
rhomboid, a gene required for dorsoventral axis establishement and peripheral nervous system development in Drosophila melanogaster.
Genes Dev
4
,
190
203
Brunner
D.
,
Ducker
K.
,
Oellers
N.
,
Hafen
E.
,
Scholz
H.
,
Klämbt
C.
(
1994
)
The ETS domain protein Pointed-P2 is a target of MAP kinase in the Sevenless signal transduction pathway.
Nature
370
,
386
389
Brunner
E.
,
Peter
O.
,
Schweizer
L.
,
Basler
K.
(
1997
)
pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.
Nature
385
,
829
833
Chou
T.-B.
,
Noll
E.
,
Perrimon
N.
(
1993
)
Autosomal P [ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras.
Development
119
,
1359
1369
Clifford
R.
,
Schupbach
T.
(
1992
)
The torpedo (DER) receptor tyrosine kinase is required at multiple times during Drosophila embryogenesis.
Development
115
,
853
872
Cohen
S. M.
(
1996
)
Controlling growth of the wing: Vestigial integrates signals from the compartment boundaries.
BioEssays
18
,
855
858
DiNardo
S.
,
Heemskerk
J.
,
Dougan
S.
,
O'Farrell
P. H.
(
1994
)
The making of a maggot: patterning the Drosophila embryonic epidermis.
Curr. Opin. Genet. Develop
4
,
529
534
Dougan
S. T.
,
DiNardo
S.
(
1992
)
wingless generates cell type diversity among engrailed expressing cells.
Nature
360
,
347
350
Freeman
M.
(
1994
)
The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor.
Mech. Dev
48
,
25
33
Freeman
M.
(
1994
)
Misexpression of the Drosophila argos gene, a secreted regulator of cell determination.
Development
120
,
2297
2304
Freeman
M.
(
1996
)
Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye.
Cell
87
,
651
660
Freeman
M.
(
1997
)
Cell determination strategies in the Drosophila eye.
Development
124
,
261
270
Freeman
M.
,
Kimmel
B. E.
,
Rubin
G. M.
(
1992
)
Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development.
Development
116
,
335
346
Freeman
M.
,
Klämbt
C.
,
Goodman
C. S.
,
Rubin
G. M.
(
1992
)
The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye.
Cell
69
,
963
975
Golembo
M.
,
Schweitzer
R.
,
Freeman
M.
,
Shilo
B.-Z.
(
1996
)
argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop.
Development
122
,
223
230
Gonzales
F.
,
Swales
L. S.
,
Bejsovec
A.
,
Skaer
H.
,
Martinez-Arias
A.
(
1991
)
Secretion and movement of wingless protein in the epidermis of the Drosophila embryo.
Mech. Dev
35
,
43
54
Hama
C.
,
Ali
Z.
,
Kornberg
T.
(
1990
)
Region-specific recombinationand expression are directed by portions of the Drosophila engrailed promoter.
Genes Dev
4
,
1079
1093
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
Heemskerk
J.
,
DiNardo
S.
(
1994
)
Drosophila hedgehog acts as a morphogen in cellular patterning.
Cell
76
,
449
460
Hill
C. S.
,
Treisman
R.
(
1995
)
Transcriptional regulation by extracellular signals: mechanisms and specificity.
Cell
80
,
199
211
Hoschuetzky
H.
,
Aberle
H.
,
Kemler
R.
(
1994
)
-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor.
J. Cell Biol
127
,
1375
1380
Ingham
P. W.
(
1993
)
Localized hedgehog activity controls spatial limits of wingless transcription in the Drosophila embryo.
Nature
366
,
560
562
Ingham
P. W.
,
Hidalgo
A.
(
1993
)
Regulation of wingless transcription in the Drosophila embryo.
Development
117
,
283
291
Kimelman
D.
,
Christian
J. L.
,
Moon
R. T.
(
1992
)
Synergistic principles of development: overlapping patterning systems in Xenopus mesoderm induction.
Development
116
,
1
9
Kolodkin
A. L.
,
Pickup
A. T.
,
Lin
D. M.
,
Goodman
C. S.
,
Banerjee
U.
(
1994
)
Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila.
Development
120
,
1731
1745
Lawrence
P. A.
,
Johnston
P.
(
1989
)
Pattern formation in the Drosophila embryo: allocation of cells to parasegments by even-skipped and fushi tarazu.
Development
105
,
761
767
Lawrence
P. A.
,
Sanson
B.
,
Vincent
J.-P.
(
1996
)
Compartments, wingless and engrailed: patterning the ventral epidermis of Drosophila embryos.
Development
122
,
4095
4103
Lee
T.
,
Feig
L.
,
Montell
D. J.
(
1996
)
Two distinct roles for Ras in a developmentally regulated cell migration.
Development
122
,
409
418
Lewis
E. B.
(
1978
)
A gene complex controlling segmentation in Drosophila.
Nature
276
,
565
570
Lohs-Schardin
M.
,
Cremer
C.
,
Nusslein-Volhard
C.
(
1979
)
A fate map of the larval epidermis of Drosophila melanogaster: localized cuticle defects following irradiation of the blastoderm with a UV laser microbeam.
Dev. Biol
73
,
239
255
Martinez-Arias
A.
,
Baker
N. E.
,
Ingham
P. W.
(
1988
)
Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo.
Development
103
,
157
170
Mayer
U.
,
Nusslein-Volhard
C.
(
1988
)
A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo.
Genes Dev
2
,
1496
1511
Neuman-Silberberg
F.
,
Schupbach
T.
(
1993
)
The Drosophila gene gurken produces a dorsally localized RNA and encodes a TGF-like protein.
Cell
75
,
165
174
Noordermeer
J.
,
Johnston
P.
,
Rijsewijk
F.
,
Nusse
R.
,
Lawrence
P. A.
(
1992
)
The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo.
Development
116
,
711
719
Nusslein-Volhard
C.
,
Wieschaus
E.
(
1980
)
Mutations affecting segment number and polarity in Drosophila.
Nature
287
,
795
801
O'Neill
E. M.
,
Rebay
I.
,
Tijan
R.
,
Rubin
G. M.
(
1994
)
The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway.
Cell
78
,
137
147
Patel
N. H.
,
Martin-Blanco
E.
,
Coleman
K. G.
,
Poole
S. J.
,
Ellis
M. C.
,
Kornberg
T. B.
,
Goodman
C. S.
(
1989
)
Expression of engrailed proteins in arthropods, annelids, and chordates.
Cell
58
,
955
968
Peifer
M.
,
Wieschaus
E.
(
1990
)
The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin.
Cell
63
,
1167
1178
Peifer
M.
,
Sweeton
D.
,
Casey
M.
,
Wieschaus
E.
(
1994
)
wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo.
Development
120
,
369
380
Perrimon
N.
(
1994
)
The genetic basis for patterned baldness in Drosophila.
Cell
76
,
781
784
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
Raz
E.
,
Shilo
B.-Z.
(
1992
)
Dissection of the faint little ball (flb) phenotype: determination of the development of the Drosophila central nervous system by early interactions in the ectoderm.
Development
114
,
113
123
Riese
J.
,
Yu
X.
,
Munnerlyn
A.
,
Eresh
S.
,
Grosschedl
R.
,
Bienz
M.
(
1997
)
LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic.
Cell
88
,
777
787
Ruohola-Baker
H.
,
Grell
E.
,
Chou
T. B.
,
Baker
D.
,
Jan
L. Y.
,
Jan
Y. N.
(
1993
)
Spatially localized rhomboid is required for establishment of the dorsal-ventral axis in Drosophila oogenesis.
Cell
73
,
953
965
Rutledge
B. J.
,
Zhang
K.
,
Bier
E.
,
Jan
Y. N.
,
Perrimon
N.
(
1992
)
The Drosophilaspitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis.
Genes Dev
6
,
1503
1517
Sampedro
J.
,
Johnston
P.
,
Lawrence
P. A.
(
1993
)
A role for wingless in the segment gradient of Drosophila?.
Development
117
,
677
687
Sánchez-Herrero
E.
,
Vernos
R.
,
Marco
R.
,
Morata
G.
(
1985
)
Genetic organisation of Drosophila bithorax complex.
Nature
313
,
108
113
Sanson
B.
,
White
P.
,
Vincent
J.-P.
(
1996
)
Uncoupling cadherin-dependent adhesion from Wingless signalling in Drosophila.
Nature
383
,
627
630
Schejter
E. D.
,
Shilo
B.-Z.
(
1989
)
The Drosophila EGF receptor homolog is allelic to faint little balll, a locus essential for embryonic development.
Cell
56
,
1093
1104
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
Schweitzer
R.
,
Howes
R.
,
Smith
R.
,
Shilo
B.-Z.
,
Freeman
M.
(
1995
)
Inhibition of Drosophila EGF receptor activation by the secreted protein Argos.
Nature
376
,
699
702
Schweitzer
R.
,
Shaharabany
M.
,
Seger
R.
,
Shilo
B.-Z.
(
1995
)
Secreted Spitz triggers the DER signalling pathway and is a limiting component in embryonic ventral ectoderm determination.
Genes Dev
9
,
1518
1529
Siegfried
E.
,
Chou
T.-B.
,
Perrimon
N.
(
1992
)
wingless signalling acts through zest-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate.
Cell
71
,
1167
1179
Simcox
A.
(
1997
)
Differential requirements for EGF-like ligands in Drosophila wing development.
Mech. Dev
62
,
41
50
Smith
J. C.
(
1993
)
Mesoderm-inducing factors in early vertebrate development.
EMBO J
12
,
4463
4470
Sturtevant
M. A.
,
Roark
M.
,
Bier
E.
(
1993
)
The Drosophilarhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signalling pathway.
Genes Dev
7
,
961
973
Sturtevant
M. A.
,
Roark
M.
,
O'Neill
J. W.
,
Biehs
B.
,
Colley
N.
,
Bier
E.
(
1996
)
The Drosophila Rhomboid protein is concentrated in patches at the apical cell surface.
Dev. Biol
174
,
298
309
Thuringer
F.
,
Cohen
S. M.
,
Bienz
M.
(
1993
)
Dissection of an indirect autoregulatory response of a homeotic Drosophila gene.
EMBO J
12
,
2419
2430
van de Wetering
M.
,
Cavallo
R.
,
Dooijes
D.
,
van Beest
M.
,
van Es
J.
,
Loureiro
J.
,
Ypma
A.
,
Hursh
D.
,
Jones
T.
,
Bejsovec
A.
,
Peifer
M.
,
Mortin
M.
,
Clevers
H.
(
1997
)
Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.
Cell
88
,
789
799
Watabe
T.
,
Kim
S.
,
Candia
A.
,
Rothbacher
U.
,
Hashimoto
C.
,
Inoue
K.
,
Cho
K. W.
(
1995
)
Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse.
Genes Dev
9
,
3038
3050
Zak
N. B.
,
Wides
R. J.
,
Schejter
E. D.
,
Raz
E.
,
Shilo
B.-Z.
(
1990
)
Localization of the DER/flb protein in embryos: implication on the faint little ball lethal phenotype.
Development
109
,
865
874
This content is only available via PDF.