The secreted proteins Wingless and Hedgehog are essential to the elaboration of the denticle pattern in the epidermis of Drosophila embryos. We show that signaling by Wingless and Hedgehog regulates the expression of veinlet (rhomboid) and Serrate, two genes expressed in prospective denticle belts. Thus, Serrate and veinlet (rhom) partake in the last layer of the segmentation cascade. Ultimately, Wingless, Hedgehog, Veinlet (an indirect activator of the Egfr) and Serrate (an activator of Notch) are expressed in non-overlapping narrow stripes. The interface between any two stripes allows a reliable prediction of individual denticle types and polarity suggesting that contact-dependent signaling modulates individual cell fates. Attributes of a morphogen can be ascribed to Hedgehog in this system. However, no single morphogen organises the whole denticle pattern.

Alexandre
C.
,
Jacinto
A.
,
Ingham
P. W.
(
1996
)
Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the Cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins.
Genes Dev
10
,
2003
2013
Baker
N. E.
(
1988
)
Embryonic and imaginal requirements for wingless, a segment-polarity gene in Drosophila.
Dev. Biol
125
,
96
108
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
Bier
E.
,
Jan
L. Y.
,
Jan
Y. N.
(
1990
)
rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster.
Genes Dev
4
,
680
681
Dickinson
W. J.
,
Thatcher
J. W.
(
1997
)
Morphogenesis of denticles and hairs in Drosophila embryos: involvement of Actin-associated proteins that also affect adult structures.
Cell Motility Cytoskel
38
,
9
21
DiNardo
S.
,
Sher
E.
,
Heemskerk-Jongens
J.
,
Kassis
J. A.
,
O'Farrell
P. H.
(
1988
)
Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis.
Nature
332
,
604
609
DiNardo
S.
,
Heemskerk
J.
,
Dougan
S.
,
O'Farrell
P. H.
(
1994
)
The making of a maggot: Patterning the Drosophila embryonic epidermis.
Curr. Opin. Genet. Dev
4
,
529
534
Dominguez
M.
,
Brunner
M.
,
Hafen
E.
,
Basler
K.
(
1996
)
Sending and receiving the Hedgehog signal: Control by the Drosophila Gli protein Cubitus interruptus.
Science
272
,
1621
1625
Dougan
S.
,
DiNardo
S.
(
1992
)
Drosophila wingless generates cell type diversity among engrailed expressing cells.
Nature
360
,
347
350
Edwards
K. A.
,
Demsky
M.
,
Montague
R. A.
,
Weymouth
N.
,
Kiehart
D. P.
(
1997
)
GFP-Moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape changes during morphogenesis in Drosophila.
Dev. Biol
191
,
103
117
Fehon
R. G.
,
Kooh
P. J.
,
Rebay
I.
,
Regan
C. L.
,
Xu
T.
,
Muskavitch
M. A.
,
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
Fietz
M. J.
,
Jacinto
A.
,
Taylor
A. M.
,
Alexandre
C.
,
Ingham
P. W.
(
1995
)
Secretion of the amino-terminal fragment of the Hedgehog protein is necessary and sufficient for hedgehog signaling in Drosophila.
Curr. Biol
5
,
643
650
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
Garcia-Bellido
A.
,
Ripoll
P.
,
Morata
G.
(
1973
)
Developmental compartmentalisation of the wing disc of Drosophila.
Nature New Biol
245
,
251
253
Gritzan
U.
,
Hatini
V.
,
DiNardo
S.
(
1999
)
Mutual antagonism between signals secreted by adjacent Wingless and Engrailed cells leads to specification of complementary regions of the Drosophila parasegment.
Development
126
,
4107
4115
Heemskerk
J.
,
DiNardo
S.
(
1994
)
Drosophila hedgehog acts as a morphogen in cellular patterning.
Cell
76
,
449
460
Hepker
J.
,
Wang
Q. T.
,
Motzny
C. K.
,
Holmgren
R.
,
Orenic
T. V.
(
1997
)
Drosophila Cubitus interruptus forms a negative feedback loop with patched and regulates expression of hedgehog target genes.
Development
124
,
549
558
Hooper
J. E.
,
Scott
M. P.
(
1989
)
The Drosophila patched gene encodes a putative membrane protein required for segmental patterning.
Cell
59
,
751
765
Ingham
P. W.
(
1988
)
The molecular genetics of embryonic pattern formation in Drosophila.
Nature
335
,
25
34
Ingham
P. W.
,
Taylor
A. M.
,
Nakano
Y.
(
1991
)
Role of the Drosophila patched gene in positional signaling.
Nature
353
,
184
187
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
Lawrence
P. A.
,
Struhl
G.
(
1996
)
Morphogens, compartments, and pattern: Lessons from Drosophila?.
Cell
85
,
951
961
Lee
J. J.
,
Von Kessler
D.
,
Parks
S.
,
Beachy
P. A.
(
1992
)
Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog.
Cell
71
,
33
50
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
Martinez-Arias
A.
,
Lawrence
P. A.
(
1985
)
Parasegments and compartments in the Drosophila embryo.
Nature
313
,
639
642
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
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
Nellen
D.
,
Burke
R.
,
Struhl
G.
,
Basler
K.
(
1996
)
Direct and long-range action of a Dpp morphogen gradient.
Cell
85
,
357
368
O'Keefe
L.
,
Dougan
S. T.
,
Gabay
L.
,
Raz
E.
,
Shilo
B. Z.
,
DiNardo
S.
(
1997
)
Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis.
Development
124
,
4837
4845
Pai
L.M.
,
Orsulic
S.
,
Bejsovec
A.
,
Peifer
M.
(
1997
)
Negativeregulation of Armadillo, a Wingless effector in Drosophila.
Development
124
,
2255
2266
Payre
F.
,
Vincent
A.
,
Carreno
S.
(
1999
)
ovo / svb integrates Wingless and DER pathways to control epidermis differentiation.
Nature
400
,
271
275
Pazdera
T.
,
Janardhan
P.
,
Minden
J.
(
1997
)
Patterned epidermal cell death in wild-type and segment polarity mutant Drosophila embryos.
Development
125
,
3427
3436
Pignoni
F.
,
Zipursky
S. L.
(
1997
)
Induction of Drosophila eye development by decapentaplegic.
Development
124
,
271
278
Poole
S. J.
,
Kauvar
L. M.
,
Drees
B.
,
Kornberg
T.
(
1985
)
The engrailed locus of Drosophila: structural analysis of an embryonic transcript.
Cell
40
,
37
43
Rutledge
B. J.
,
Zhang
K.
,
Bier
E.
,
Jan
Y. N.
,
Perrimon
N.
(
1992
)
The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis.
Genes Dev
6
,
1503
1517
Sanson
B.
,
White
P.
,
Vincent
J. P.
(
1996
)
Uncoupling Cadherin-based adhesion from Wingless signaling in Drosophila.
Nature
383
,
627
630
Sanson
B.
,
Alexandre
C.
,
Fascetti
N.
,
Vincent
J.-P.
(
1999
)
Engrailed and Hedgehog make the range of Wingless asymmetric in Drosophila embryos.
Cell
98
,
207
216
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.
,
Shaharabany
M.
,
Seger
R.
,
Shilo
B. Z.
(
1995
)
Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination.
Genes Dev
9
,
1518
1529
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
Struhl
G.
,
Fitzgerald
K.
,
Greenwald
I.
(
1993
)
Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.
Cell
74
,
331
345
Szuts
D.
,
Freeman
M.
,
Bienz
M.
(
1997
)
Antagonism between EGFR and Wingless signaling in the larval cuticle of Drosophila.
Development
124
,
3209
3219
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
Vincent
J. P.
,
O'Farrell
P. H.
(
1992
)
The state of engrailed expression is not clonally transmitted during early Drosophila development.
Cell
68
,
923
931
Wiellette
E. L.
,
McGinnis
W.
(
1999
)
Hox genes differentially regulate Serrate to generate segment-specific structures.
Development
126
,
1985
1995
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