During neurogenesis, the transmembrane protein Patched (Ptc) promotes a wingless (wg)-mediated specification of a neuronal precursor cell, NB4-2, by repressing gooseberry (gsb). In this study, novel interactions of these genes with engrailed (en) and invected (inv) during neurogenesis have been uncovered. While in row 4 cells Ptc represses gsb and wg, in row 5 cells en/inv relieve Ptc repression of gsb by a non-autonomous mechanism that does not involve hedgehog (hh). This differential regulation of gsb leads to the specification of NB5-3 and NB4-2 identities to two distinct neuroblasts. The uncoupling of the ptc-gsb regulatory circuit also enables gsb to promote Wg expression in row 5 cells. Our results suggest that the en/inv-->ptc-->gsb-->wg pathway uncovered here and the hh-->wg are distinct pathways that function to maintain wild-type level of Wg. Our results also indicate that Hh is not the only ligand for Ptc and similarly Ptc is not the only receptor for Hh.

REFERENCES

Alcedo
J.
,
Ayzenzo
M.
,
von Ohlen
T.
,
Noll
M.
,
Hooper
J.E.
(
1996
)
The Drosophilasmoothened gene encodes a seven-pass membrane protein, a putative receptor for the Hedgehog signal.
Cell
86
,
221
232
Bate
C. M.
(
1976
)
Embryogenesis of an insect nervous system. I. A map of the thoracic and abdominal neuroblasts in Locusta migratoria.
J. Embryol. Exp. Morphol
35
,
107
123
Bejsovec
A.
,
Wieschaus
E.
(
1993
)
Segment polarity gene interactionsmodulate epidermal patterning in Drosophila embryos.
Development
119
,
501
517
Bhat
K. M.
(
1996
)
The patched signaling pathway mediates repression of gooseberry allowing neuroblast specification by wingless during Drosophila neurogenesis.
Development
122
,
2921
2932
Bhat
K. M.
,
Schedl
P.
(
1994
)
The Drosophilamitimere gene a member of the POU family is required for the specification of the RP2/sibling lineage during neurogenesis.
Development
120
,
1501
1519
Bhat
K. M.
,
Poole
S. J.
,
Schedl
P.
(
1995
)
mitimere and pdm1 genes collaborate during specification of the RP2/sib lineage in Drosophila neurogenesis.
Mol. Cell. Biol
15
,
4052
4063
Bossing
T.
,
Udolph
G.
,
Doe
C. Q.
,
Technau
G. M.
(
1996
)
The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm.
Dev. Biol
179
,
41
64
Cabrera
C. V.
(
1992
)
The generation of cell diversity during early neurogenesis in Drosophila.
Development
115
,
893
901
Chen
Y.
,
Struhl
G.
(
1996
)
Dual roles for Patched in sequestering and transducing Hedgehog.
Cell
87
,
553
563
Chu-LaGraff
Q.
,
Doe
C. Q.
(
1993
)
Neuroblast specification and formation regulated by wingless in the Drosophila CNS.
Science
261
,
1594
1597
Chu-LaGraff
Q.
,
Schmid
A.
,
Leidel
J.
,
Bronner
G.
,
Jackle
H.
,
Doe
C.Q.
(
1995
)
huckenbein specifies aspects of CNS precursor identity required for axon pathfinding and target recognition.
Neuron
15
,
1041
1051
Doe
C.Q.
(
1992
)
Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system.
Development
116
,
855
863
Gustavson
E.
,
Goldsborough
A. S.
,
Ali
Z.
,
Kornberg
T. B.
(
1996
)
The Drosophilaengrailed and invected genes: parameters in regulation, expression, and function.
Genetics
142
,
893
906
Hidalgo
A.
(
1991
)
Interactions between segment polarity genes and the generation of the segmental pattern in Drosophila.
Mech. Dev
35
,
77
87
Hooper
J. E.
(
1995
)
Distinct pathways for autocrine and paracrine wingless signaling in Drosophila embryos.
Nature
372
,
461
464
Hooper
J. E.
,
Scott
M. P.
(
1989
)
The Drosophilapatched gene encodes a putative membrane protein required for segmental patterning.
Cell
59
,
751
765
Ingham
P. W.
(
1995
)
Signaling by hedgehog family proteins in Drosophila a nd vertebrate development.
Curr. Opin. Genet. Dev
5
,
492
498
Ingham
P.W.
,
Taylor
A.M.
,
Nakano
Y.
(
1991
)
Role of the Drosophila patched gene in positional signaling.
Nature
353
,
184
187
Ingham
P.W.
,
Hidalgo
A.
(
1993
)
Regulation of wingless transcription in the Drosophila embryo.
Development
117
,
283
291
Klingensmith
J.
,
Nusse
R.
(
1994
)
Signaling by wingless in Drosophila.
Dev. Biol
166
,
396
414
Li
X.
,
Noll
M.
(
1993
)
Role of gooseberry gene in Drosophila embryos: maintenance of wingless expression by a wingless-gooseberry autoregulatory loop.
EMBO J
12
,
4499
4509
Li
X.
,
Noll
M.
(
1994
)
Evolution of distinct developmental functions of three Drosophila genes by acquisition of different cis-regulatory regions.
Nature
367
,
83
87
Martinez-Arias
A.
,
Bake.
N.E.
,
Ingham
P.W.
(
1988
)
Role of segement polarity genes in the definition and maintenance of cell states in the Drosophila embryo.
Development
103
,
157
170
Marigo
V.
,
Davey
R. A.
,
Zuo
Y.
,
Cunningham
J. M.
,
Tabin
C. J.
(
1996
)
Biochemical evidence that Patched is the Hedgehog receptor.
Nature
384
,
176
179
Matsuzaki
M.
,
Saigo
K.
(
1996
)
hedgehog signaling independent of engrailed and wingless required for post-S1 neuroblast formation in Drosophila CNS.
Development
122
,
3567
3575
Nakano
Y.
,
Guerrero
I.
,
Hidalgo
A.
,
Taylor
A. M.
,
Whittle
J. R. S.
,
Ingham
P. W.
(
1989
)
The Drosophila segment polarity gene patched encodes a protein with multiple potential membrane spanning domains.
Nature
341
,
508
513
Noordermeer
J.
,
Johnson
P.
,
Rijsewijk
F.
,
Nusse
R.
,
Lawrence
P.
(
1992
)
The consequences of ubiquitous expression of the wingless gene in the Drosophila embryos.
Development
116
,
711
719
Patel
N. H.
,
Schafer
B.
,
Goodman
C. S.
,
Holmgren
R.
(
1989
)
The roleof segment polarity genes during Drosophila neurogenesis.
Genes Dev
3
,
890
904
Perrimon
N.
(
1996
)
Serpentine proteins slither into the wingless and hedgehog fields.
Cell
86
,
513
516
Porter
J. A.
,
Young
K. E.
,
Beachy
P. A.
(
1996
)
Cholesterol modification of Hedgehog signaling proteins in animal development.
Science
274
,
255
259
Prokop
A.
,
Technau
G. M.
(
1994
)
Early tagma specific commitment of Drosophila CNS progenitor NB1-1.
Development
120
,
2567
2578
Schuske
K.
,
Hooper
J. E.
,
Scott
M. P.
(
1994
)
patched overexpression causes loss of wingless expression in Drosophila embryos.
Dev. Biol
164
,
300
311
Skeath
J. B.
,
Zhang
Y.
,
Holmgren
R.
,
Carroll
S. B.
,
Doe
C. Q.
(
1995
)
Specification of neuroblasts identity in the Drosophila embryonic central nervous system by the gooseberry-distal gene.
Nature
376
,
427
430
Stone
D. M.
,
Hynes
M.
,
Armanini
M.
,
Swanson
T. A.
,
Gu
Q.
,
Johnson
R. L.
,
Scott
M. P.
,
Pennica
D.
,
Goddard
A.
,
Philips
H.
,
Noll
M.
,
Hooper
J. E.
,
de Sauvage
F.
,
Rosenthal
A.
(
1996
)
The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
Nature
384
,
129
134
Tabata
T.
,
Eaton
S. E.
,
Kornberg
T. B.
(
1992
)
The Drosophila hedgehog gene is expressed in posterior compartment cells and is a target of engrailed regulation.
Genes Dev
6
,
2635
2645
Thomas
J. B.
,
Bastiani
M. J.
,
Bate
M.
,
Goodman
C. S.
(
1984
)
From grasshopper to Drosophila: a common plan for neuronal development.
Nature
310
,
203
207
Udolph
G.
,
Luer
K.
,
Bossing
T.
,
Technau
G. M.
(
1995
)
Commitment of CNS progenitors along the dorsoventral axis of Drosophila neuroectoderm.
Science
269
,
1278
1281
Udolph
G.
,
Prokop
A.
,
Bossing
T.
,
Technau
G. M.
(
1993
)
A common precursor for glia and neurons in the embryonic CNS of Drosophila gives rise to segment-specific lineage variants.
Development
118
,
765
775
van den Heuvel
M.
,
Ingham
P.W.
(
1996
)
smoothened encodes a receptor-like serpentine protein required for hedgehog signaling.
Nature
382
,
547
551
Zhang
Y.
,
Ungar
A.
,
Fresquez
C.
,
Holmgren
R.
(
1994
)
Ectopic expression of either the Drosophila gooseberry-distal or proximal gene causes alterations of cell fate in the epidermis and central nervous system.
Development
120
,
1151
1161
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