The adult peripheral nervous system of Drosophila includes a complex array of mechanosensory organs (bristles) that cover much of the body surface of the fly. The four cells (shaft, socket, sheath, and neuron) which compose each of these organs adopt distinct fates as a result of cell-cell signaling via the Notch (N) pathway. However, the specific mechanisms by which these cells execute their conferred fates are not well understood. Here we show that D-Pax2, the Drosophila homolog of the vertebrate Pax2 gene, has an essential role in the differentiation of the shaft cell. In flies bearing strong loss-of-function mutations in the shaven function of D-Pax2, shaft structures specifically fail to develop. Consistent with this, we find that D-Pax2 protein is expressed in all cells of the bristle lineage during the mitotic (cell fate specification) phase of bristle development, but becomes sharply restricted to the shaft and sheath cells in the post-mitotic (differentiative) phase. Two lines of evidence described here indicate that D-Pax2 expression and function is at least in part downstream of cell fate specification mechanisms such as N signaling. First, we find that the lack of late D-Pax2 expression in the socket cell (the sister of the shaft cell) is controlled by N pathway activity; second, we find that loss of D-Pax2 function is epistatic to the socket-to-shaft cell fate transformation caused by reduced N signaling. Finally, we show that misexpression of D-Pax2 is sufficient to induce the production of ectopic shaft structures. From these results, we propose that D-Pax2 is a high-level transcriptional regulator of the shaft cell differentiation program, and acts downstream of the N signaling pathway as a specific link between cell fate determination and cell differentiation in the bristle lineage.

Reference

Bailey
A. M.
,
Posakony
J. W.
(
1995
)
Suppressor of Hairless directly activates transcription of Enhancer of split Complex genes in response to Notch receptor activity.
Genes Dev
9
,
2609
2622
Bang
A. G.
,
Posakony
J. W.
(
1992
)
The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development.
Genes Dev
6
,
1752
1769
Bang
A. G.
,
Bailey
A. M.
,
Posakony
J. W.
(
1995
)
Hairless promotes stable commitment to the sensory organ precursor cell fate by negatively regulating the activity of the Notch signaling pathway.
Dev. Biol
172
,
479
494
Bang
A. G.
,
Hartenstein
V.
,
Posakony
J. W.
(
1991
)
Hairless is required for the development of adult sensory organ precursor cells in Drosophila.
Development
111
,
89
104
Bellen
H. J.
,
O'Kane
C. J.
,
Wilson
C.
,
Grossniklaus
U.
,
Pearson
R. K.
,
Gehring
W. J.
(
1989
)
P-element-mediated enhancer detection: a versatile method to study development in Drosophila.
Genes Dev
3
,
1288
1300
Bier
E.
,
Väessin
H.
,
Shepherd
S.
,
Lee
K.
,
McCall
K.
,
Barbel
S.
,
Ackerman
L.
,
Carretto
R.
,
Uemura
T.
,
Grell
E.
, et al. 
(
1989
)
Searching for pattern and mutation in the Drosophila genome with a P- lacZ vector.
Genes Dev
3
,
1273
1287
Brand
A. H.
,
Manoukian
A. S.
,
Perrimon
N.
(
1994
)
Ectopic expression in Drosophila.
Methods Cell Biol
44
,
635
654
Brand
A. H.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
Brou
C.
,
Logeat
F.
,
Lecourtois
M.
,
Vandekerckhove
J.
,
Kourilsky
P.
,
Schweisguth
F.
,
Israel
A.
(
1994
)
Inhibition of the DNA-binding activity of Drosophila Suppressor of Hairless and of its human homolog, KBF2/RBP-J, by direct protein-protein interaction with Drosophila Hairless.
Genes Dev
8
,
2491
2503
Burrill
J. D.
,
Moran
L.
,
Goulding
M. D.
,
Saueressig
H.
(
1997
)
PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+interneurons that require PAX6 for their development.
Development
124
,
4493
4503
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
Dahl
E.
,
Koseki
H.
,
Balling
R.
(
1997
)
Pax genes and organogenesis.
BioEssays
19
,
755
765
FlyBase
(
1998
)
FlyBase—A Drosophila database.
Nucleic Acids Res
26
,
85
88
Fortini
M. E.
,
Artavanis-Tsakonas
S.
(
1994
)
The Suppressor of Hairless protein participates in Notch receptor signaling.
Cell
79
,
273
282
Frise
E.
,
Knoblich
J. A.
,
Younger-Shepherd
S.
,
Jan
L. Y.
,
Jan
Y. N.
(
1996
)
The Drosophila Numb protein inhibits signaling of the Notch receptor during cell-cell interaction in sensory organ lineage.
Proc. Natl. Acad. Sci. USA
93
,
11925
11932
Fu
W.
,
Duan
H.
,
Frei
E.
,
Noll
M.
(
1998
)
shaven and sparkling are mutations in separate enhancers of the Drosophila Pax2 homolog.
Development
125
,
2943
2950
Fu
W.
,
Noll
M.
(
1997
)
The Pax2 homolog sparkling is required for development of cone and pigment cells in the Drosophila eye.
Genes Dev
11
,
2066
2078
Furukawa
T.
,
Maruyama
S.
,
Kawaichi
M.
,
Honjo
T.
(
1992
)
The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development.
Cell
69
,
1191
1197
Greenwald
I.
(
1998
)
LIN-12/Notch signaling: lessons from worms and flies.
Genes Dev
12
,
1751
1762
Guo
M.
,
Jan
L. Y.
,
Jan
Y. N.
(
1996
)
Control of daughter cell fates during asymmetric division: Interaction of Numb and Notch.
Neuron
17
,
27
41
Hartenstein
V.
,
Posakony
J. W.
(
1989
)
Development of adult sensilla on the wing and notum of Drosophila melanogaster.
Development
107
,
389
405
Hartenstein
V.
,
Posakony
J. W.
(
1990
)
Sensillum development in the absence of cell division: the sensillum phenotype of the Drosophila mutant string.
Dev. Biol
138
,
147
158
Higashijima
S.
,
Michiue
T.
,
Emori
Y.
,
Saigo
K.
(
1992
)
Subtype determination of Drosophila embryonic external sensory organs by redundant homeo box genes BarH1 and BarH2.
Genes Dev
6
,
1005
1018
Hochman
B.
(
1971
)
Analysis of chromosome 4 in Drosophila melanogaster. II. Ethyl methanesulfonate induced lethals.
Genetics
67
,
235
252
Huang
F.
,
Dambly-Chaudiere
C.
,
Ghysen
A.
(
1991
)
The emergence of sense organs in the wing disc of Drosophila.
Development
111
,
1087
1095
Jarriault
S.
,
Brou
C.
,
Logeat
F.
,
Schroeter
E. H.
,
Kopan
R.
,
Israel
A.
(
1995
)
Signalling downstream of activated mammalian Notch.
Nature
377
,
355
358
Kimble
J.
,
Simpson
P.
(
1997
)
The LIN-12/Notch signaling pathway and its regulation.
Ann. Rev. Cell Dev. Biol
13
,
333
361
Lecourtois
M.
,
Schweisguth
F.
(
1995
)
The neurogenic Suppressor of Hairless DNA-binding protein mediates the transcriptional activation of the Enhancer of split Complex genes triggered by Notch signaling.
Genes Dev
9
,
2598
2608
Lecourtois
M.
,
Schweisguth
F.
(
1998
)
Indirect evidence for Delta-dependent intracellular processing of Notch in Drosophila embryos.
Curr. Biol
8
,
771
774
Lees
A. D.
,
Waddington
C. H.
(
1942
)
The development of the bristlesin normal and some mutant types of Drosophila melanogaster.
Proc. Roy. Soc. Ser. B
131
,
87
110
Lewis
E. B.
,
Bacher
F.
(
1968
)
Methods of feeding ethyl methane sulfonate (EMS) to Drosophila males.
Dros. Inf. Serv
43
,
193
–.
Lyman
D. F.
,
Yedvobnick
B.
(
1995
)
Drosophila Notch receptor activity suppresses Hairless function during adult external sensory organ development.
Genetics
141
,
1491
1505
Milán
M.
,
Diaz-Benjumea
F. J.
,
Cohen
S. M.
(
1998
)
Beadex encodes an LMO protein that regulates Apterous LIM-homeodomain activity in Drosophila wing development: a model for LMO oncogene function.
Genes Dev
12
,
2912
2920
Noll
M.
(
1993
)
Evolution and role of Pax genes.
Curr. Biol
3
,
595
605
O'Neill
E. M.
,
Rebay
I.
,
Tjian
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
Otteson
D. C.
,
Shelden
E.
,
Jones
J. M.
,
Kameoka
J.
,
Hitchcock
P. F.
(
1998
)
Pax2 expression and retinal morphogenesis in the normal and Krd mouse.
Dev. Biol
193
,
209
224
Phelps
C. B.
,
Brand
A. H.
(
1998
)
Ectopic gene expression in Drosophila using GAL4 system.
Methods
14
,
367
379
Posakony
J. W.
(
1994
)
Nature versus nurture: asymmetric cell divisions in Drosophila bristle development.
Cell
76
,
415
418
Price
B. D.
,
Chang
Z.
,
Smith
R.
,
Bockheim
S.
,
Laughon
A.
(
1993
)
The Drosophila neuralized gene encodes a C3HC4 zinc finger.
EMBO J
12
,
2411
2418
Rhyu
M. S.
,
Jan
L. Y.
,
Jan
Y. N.
(
1994
)
Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells.
Cell
76
,
477
491
Robinow
S.
,
White
K.
(
1988
)
The locus elav of Drosophila melanogaster is expressed in neurons at all developmental stages.
Dev. Biol
126
,
294
303
Roseman
R. R.
,
Johnson
E. A.
,
Rodesch
C. K.
,
Bjerke
M.
,
Nagoshi
R. N.
,
Geyer
P. K.
(
1995
)
A P element containing suppressor of Hairy-wing binding regions has novel properties for mutagenesis in Drosophila melanogaster.
Genetics
141
,
1061
1074
Rubin
G. M.
,
Spradling
A. C.
(
1982
)
Genetic transformation of Drosophila with transposable element vectors.
Science
218
,
348
353
Schroeter
E. H.
,
Kisslinger
J. A.
,
Kopan
R.
(
1998
)
Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.
Nature
393
,
382
386
Schweisguth
F.
,
Posakony
J. W.
(
1992
)
Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates.
Cell
69
,
1199
1212
Schweisguth
F.
,
Posakony
J. W.
(
1994
)
Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis.
Development
120
,
1433
1441
Struhl
G.
,
Adachi
A.
(
1998
)
Nuclear access and action of Notch in vivo.
Cell
93
,
649
660
Tamura
K.
,
Taniguchi
Y.
,
Minoguchi
S.
,
Sakai
T.
,
Tun
T.
,
Furukawa
T.
,
Honjo
T.
(
1995
)
Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J/Su(H).
Curr. Biol
5
,
1416
1423
Toney
J. V.
,
Thompson
J. N.
(
1980
)
Developmental control of the orientation of cuticular structures in Drosophila.
Experientia
36
,
644
645
Torres
M.
,
Giráldez
F.
(
1998
)
The development of the vertebrate inner ear.
Mech. Dev
71
,
5
21
Torres
M.
,
Gomez-Pardo
E.
,
Dressler
G. R.
,
Gruss
P.
(
1995
)
Pax-2 controls multiple steps of urogenital development.
Development
121
,
4057
4065
Urbánek
P.
,
Fetka
I.
,
Meisler
M. H.
,
Busslinger
M.
(
1997
)
Cooperation of Pax2 and Pax5 in midbrain and cerebellum development.
Proc. Natl. Acad. Sci. USA
94
,
5703
5708
Zipursky
S. L.
,
Venkatesh
T. R.
,
Teplow
D. B.
,
Benzer
S.
(
1984
)
Neuronal development in the Drosophila retina: Monoclonal antibodies as molecular probes.
Cell
36
,
15
26
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