During eye development in Drosophila, cell cycle progression is coordinated with differentiation. Prior to differentiation, cells arrest in G1 phase anterior to and within the morphogenetic furrow. We show that Decapentaplegic (Dpp), a TGF-β family member, is required to establish this G1 arrest, since Dpp-unresponsive cells located in the anterior half of the morphogenetic furrow show ectopic S phases and ectopic expression of the cell cycle regulators Cyclins A, E and B. Conversely, ubiquitous over-expression of Dpp in the eye imaginal disc transiently inhibits S phase without affecting Cyclin E or Cyclin A abundance. This Dpp-mediated inhibition of S phase occurs independently of the Cyclin A inhibitor Roughex and of the expression of Dacapo, a Cyclin E-Cdk2 inhibitor. Furthermore, Dpp-signaling genes interact genetically with a hypomorphic cyclin E allele. Taken together our results suggest that Dpp acts to induce G1 arrest in the anterior part of the morphogenetic furrow by a novel inhibitory mechanism. In addition, our results provide evidence for a Dpp-independent mechanism that acts in the posterior part of the morphogenetic furrow to maintain G1 arrest.

Alevizopoulos
A.
,
Mermod
N.
(
1997
)
Transforming growth factor-: the breaking open of a black box.
BioEssays
19
,
581
591
Borod
E. R.
,
Heberlein
U.
(
1998
)
Mutual regulation of decapentaplegic and hedgehog during the initiation of differentiation in the Drosophila retina.
Dev. Biol
197
,
187
197
Brand
A. H.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
Campbell
G.
,
Tomlinson
A.
(
1995
)
Initiation of the proximodistal axis in insect legs.
Development
121
,
619
628
Capdevila
J.
,
Guerrero
I.
(
1994
)
Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings.
EMBO J
13
,
4459
4468
Chanut
F.
,
Heberlein
U.
(
1997
)
Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina.
Development
124
,
559
567
de Nooij
J. C.
,
Hariharan
I. K.
(
1995
)
Uncoupling cell fate determination from patterned cell division in the Drosophila eye.
Science
270
,
983
985
de Nooij
J. C.
,
Letendre
M. A.
,
Hariharan
I. K.
(
1996
)
A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis.
Cell
87
,
1237
1247
Edgar
B. A.
,
Datar
S. A.
(
1996
)
Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila ‘s early cell cycle program.
Genes Dev
10
,
1966
1977
Follette
P. J.
,
O'Farrell
P. H.
(
1997
)
Connecting cell behaviour to patterning: lessons from the cell cycle.
Cell
88
,
309
314
Follette
P. J.
,
O'Farrell
P. H.
(
1997
)
Cdks and the Drosophila cell cycle.
Curr. Opin. Genet. Dev
7
,
17
22
Gao
C. Y.
,
Zelenka
P. S.
(
1997
)
Cyclins, cyclin-dependent kinases and differentiation.
BioEssays
19
,
307
315
Heberlein
U.
,
Moses
K.
(
1995
)
Mechanisms of Drosophila retinal morphogenesis: the virtues of being progressive.
Cell
81
,
987
990
Lane
M. E.
,
Sauer
K.
,
Wallace
K.
,
Jan
Y. N.
,
Lehner
C.
,
Vaessin
H.
(
1996
)
Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development.
Cell
87
,
1225
1235
Lehner
C. F.
,
Lane
M. E.
(
1997
)
Cell cycle regulators in Drosophila: downstream and part of developmental decisions.
J. Cell Sci
110
,
523
528
Ma
C.
,
Zhou
Y.
,
Beachy
P. A.
,
Moses
K.
(
1993
)
The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye.
Cell
75
,
927
938
Massague
J.
,
Polyak
K.
(
1995
)
Mammalian antiproliferative signals and their targets.
Curr. Opin. Genet. Dev
5
,
91
96
Massague
J.
(
1996
)
TGF-signaling: receptors, transducers and Mad proteins.
Cell
85
,
947
950
Masucci
J. D.
,
Miltenberger
R. J.
,
Hoffman
F. M.
(
1990
)
Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal discs is regulated by 3cis-regulatory elements.
Genes Dev
4
,
2011
2023
Nigg
E. A.
(
1995
)
Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle.
BioEssays
17
,
471
480
Penton
A.
,
Selleck
S. B.
,
Hoffman
F. M.
(
1997
)
Regulation of cell cycle synchronization by decapentaplegic during Drosophila eye development.
Science
275
,
203
206
Richardson
H.
,
O'Keefe
L.
,
Marty
T.
,
Saint
R.
(
1995
)
Ectopic Cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc.
Development
121
,
3371
3379
Secombe
J.
,
Pispa
J.
,
Saint
R.
,
Richardson
H.
(
1998
)
Analysis of a Drosophilacyclin E hypomorphic mutation suggests a novel role for Cyclin E in cell proliferation.
Genetics
149
,
1867
1882
Singer
M. A.
,
Penton
A.
,
Twombly
V.
,
Hoffman
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
Sprenger
F.
,
Yakubovich
N.
,
O'Farrell
P. H.
(
1997
)
S-phase function of Drosophila cyclin A and its downregulation in G1 phase.
Curr. Biol
7
,
488
499
Thomas
B. J.
,
Gunning
D. A.
,
Cho
J.
,
Zipursky
S. L.
(
1994
)
Cell cycle progression in the developing Drosophila eye: roughex encodes a novel protein required for the establishment of G1.
Cell
77
,
1003
1014
Thomas
B. J.
,
Zavitz
K. H.
,
Dong
X.
,
Lane
M. E.
,
Weigmann
K.
,
Finley
R. L.
,
Brent
R.
,
Lehner
C.
,
Zipursky
S. L.
(
1997
)
roughex down-regulates G2 cyclins in G1.
Genes Dev
11
,
1289
1298
Tsuneizumi
K.
,
Nakayama
T.
,
Kamoshida
Y.
,
Kornberg
T. B.
,
Christian
J. L.
,
Tabata
T.
(
1997
)
Daughters-against-dpp modulates dpp organising activity in Drosophila wing development.
Nature
389
,
627
631
Wall
N. A.
,
Hogan
B. L. M.
(
1994
)
TGF-related genes in development.
Curr. Opin. Genet. Dev
4
,
517
522
Xu
T.
,
Rubin
G. M.
(
1993
)
Analysis of genetic mosaics in developing and adult Drosophila tissues.
Development
117
,
1223
1237
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