The Drosophila gene torpedo/Egfr (top/Egfr) encodes a homolog of the vertebrate Epidermal Growth Factor receptor. This receptor is required several times during the life cycle of the fly for the transmisson of developmental cues. During oogenesis, Top/Egfr activation is required for the establishment of the dorsal/ventral axis of the egg and the embryo. To examine how ectopic Top/Egfr activation affects cell fate determination, we constructed an activated version of the protein. Expression of this activated form (lambda top) in the follicle cells of the ovary induces dorsal cell fates in both the follicular epithelium and the embryo. Different levels of expression resulted in different dorsal follicle cell fates. These dorsal cell fates were expanded in the anterior, but not the posterior, of the egg, even in cases where all the follicle cells covering the oocyte expressed lambda top. The expression of genes known to respond to top/Egfr activation, argos (aos), kekkon1 (kek 1) and rhomboid (rho), was also expanded in the presence of the lambda top construct. When lambda top was expressed in all the follicle cells covering the oocyte, kek 1 and argos expression was induced in follicle cells all along the anterior/posterior axis of the egg chamber. In contrast, rho RNA expression was only activated in the anterior of the egg chamber. These data indicate that the response to Top/Egfr signaling is regulated by an anterior/posterior prepattern in the follicle cells. Expression of lambda top in the entire follicular epithelium resulted in an embryo dorsalized along the entire anterior/posterior axis. Expression of lambda top in anterior or posterior subpopulations of follicle cells resulted in regionally autonomous dorsalization of the embryos. This result indicates that subpopulations of follicle cells along the anterior/posterior axis can respond to Top/Egfr activation independently of one another.

REFERENCES

Baker
N. E.
,
Rubin
G. M.
(
1992
)
Ellipse mutations in the Drosophila homologue of the EGF receptor affect pattern formation, cell division, and cell death in eye imaginal discs.
Dev. Biol
150
,
381
396
Basler
K.
,
Christen
B.
,
Hafen
E.
(
1991
)
Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye.
Cell
64
,
1069
1081
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
,
190
203
Brand
A.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
Brand
A. H.
,
Perrimon
N.
(
1994
)
Raf acts downstream of the EGFreceptor to determine dorsoventral polarity during Drosophila oogenesis.
Genes Dev
8
,
629
639
Brunner
D.
,
Oellers
N.
,
Szabad
J.
,
Biggs III
W. H.
,
Zipursky
S. L.
,
Hafen
E.
(
1994
)
A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways.
Cell
76
,
875
888
Clifford
R. J.
,
Schupbach
T.
(
1989
)
Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene.
Genetics
123
,
771
787
Diaz-Benjumea
F. J.
,
Garcia-Bellido
A.
(
1990
)
Behaviour of cells mutant for an EGF receptor homologue of Drosophila in genetic mosaics.
Proc. R. Soc. Lond. B,
242
,
36
44
Duffy
J. B.
,
Perrimon
N.
(
1996
)
Recent advances in understanding signal transduction pathways in worms and flies.
Current Opinion in Cell Biology
8
,
231
238
Fantl
W. J.
,
Johnson
D. E.
,
Williams
L. T.
(
1993
)
Signalling by receptor tyrosine kinases.
Annu. Rev. Biochem
62
,
453
481
Freeman
M.
(
1997
)
Cell determination strategies in the Drosophila eye.
Development
124
,
261
270
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
Gonzalez-Reyes
A.
,
Elliott
H.
,
St Johnston
D.
(
1995
)
Polarization of both major body axes in Drosophila by gurken-torpedo signalling.
Nature
375
,
654
658
Harrison
D. A.
,
Binari
R.
,
Nahreini
T. S.
,
Gilman
M.
,
Perrimon
N.
(
1995
)
Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects.
EMBO J
14
,
2857
2865
Hsu
T.
,
Bagni
C.
,
Sutherland
J. D.
,
Kafatos
F. C.
(
1996
)
The transcription factor CF2 is a mediator of EGF-R-activated dorsoventral patterning in Drosophila oogenesis.
Genes Dev
10
,
1411
1421
Hunter
T.
(
1997
)
Oncoprotein Networks.
Cell
88
,
333
346
Kammermeyer
K. L.
,
Wadsworth
S. C.
(
1987
)
Expression of Drosophila epidermal growth factor receptor homologue in mitotic cell populations.
Development
100
,
201
210
Lee
T.
,
Hacohen
N.
,
Krasnow
M.
,
Montell
D.
(
1996
)
Regulated breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system.
Genes Dev
10
,
2912
2921
Livneh
E.
,
Glazer
L.
,
Segal
D.
,
Schlessinger
J.
,
Shilo
B.-Z.
(
1985
)
The Drosophila EGF receptor gene homolog: conservation of both hormone binding and kinase domains.
Cell
40
,
599
607
Morimoto
A. M.
,
Jordan
K. C.
,
Tietze
K.
,
Britton
J. S.
,
O'Neill
E. M.
,
Ruohola-Baker
H.
(
1996
)
Pointed, an ETS domain transcription factor, negatively regulates the EGF receptor pathway in Drosophila oogensis.
Development
122
,
3745
3754
Morisato
D.
,
Anderson
K.
(
1995
)
Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo.
Annu. Rev. Genetics
29
,
371
399
Musacchio
M.
,
Perrimon
N.
(
1996
)
The Drosophila kekkon genes: novel members of both the leucine-rich repeat and immunoglobulin superfamilies expressed in the CNS.
Dev. Biol
178
,
63
76
Neuman-Silberberg
F. S.
,
Schupbach
T.
(
1993
)
The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGF-like protein.
Cell
75
,
165
174
Price
J. V.
,
Clifford
R. J.
,
Schupbach
T.
(
1989
)
The maternal ventralizing locus torpedo is allelic to faint little ball, an embryonic lethal, encodes the Drosophila EGF receptor homolog.
Cell
56
,
1085
1092
Ray
R. P.
,
Schupbach
T.
(
1996
)
Intercellular signaling and the polarization of body axes during Drosophila oogenesis.
Genes Dev
10
,
1711
1723
Raz
E.
,
Schejter
E. D.
,
Shilo
B.-Z.
(
1991
)
Interallelic complementation among DER/flb alleles: implications for the mechanism of signal transduction by receptor tyrosine kinases.
Genetics
129
,
191
201
Roth
S.
,
Neuman-Silberberg
F. S.
,
Barcelo
G.
,
Schupbach
T.
(
1995
)
cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila.
Cell
81
,
967
978
Roth
S.
,
Stein
D.
,
Nusslein-Volhard
C.
(
1989
)
A gradient of nuclearlocalization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo.
Cell
59
,
1189
1202
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
Schejter
E. D.
,
Shilo
B.-Z.
(
1989
)
The Drosophila EGF receptor homolog (DER) gene is allelic to faint little ball, a locus essential for embryonic development.
Cell
56
,
1093
1104
Schlessinger
J.
,
Ullrich
A.
(
1992
)
Growth factor signaling by receptor tyrosine kinases.
Neuron
9
,
383
391
Schupbach
T.
(
1987
)
Germ line and soma cooperate during oogenesis to establish the dorsoventral pattern of egg shell and embryo in Drosophila melanogaster.
Cell
49
,
699
707
Schweitzer
R.
,
Shilo
B.-Z.
(
1997
)
A thousand and one roles for the Drosophila EGF receptor.
Trends in Genetics
13
,
191
196
Tautz
D.
,
Pfeifle
C.
(
1989
)
A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback.
Chromosoma
98
,
81
85
Twombly
V.
,
Blackman
R. K.
,
Jin
H.
,
Graff
J. M.
,
Padgett
R. W.
,
Gelbart
W. M.
(
1996
)
The TGF-signaling pathway is essential for Drosophila oogenesis.
Development
122
,
1555
1565
Wadsworth
S. C.
,
Vincent III
W. S.
,
Bilodeau-Wentworth
D.
(
1985
)
A Drosophila genomic sequence with homology to the human epidermal growth factor receptor.
Nature
314
,
178
180
This content is only available via PDF.