The Drosophila ventral midline cells generate a discrete set of CNS lineages, required for proper patterning of the ventral ectoderm. Here we provide the first evidence that the CNS midline cells also exert inductive effects on the mesoderm. Mesodermal progenitors adjacent to the midline progenitor cells give rise to ventral somatic mucles and a pair of unique cells that come to lie dorsomedially on top of the ventral nerve cord, the so-called DM cells. Cell ablation as well as cell transplantation experiments indicate that formation of the DM cells is induced by midline progenitors in the early embryo. These results are corroborated by genetic analyses. Mutant single minded embryos lack the CNS midline as well as the DM cells. Embryos mutant for any of the spitz group genes, which primarily express defects in the midline glial cell lineages, show reduced formation of the DM cells. Conversely, directed overexpression of secreted SPITZ by some or all CNS midline cells leads to the formation of additional DM cells. Furthermore we show that DM cell development does not depend on the absolute concentration of a local inductor but appears to require a graded source of an inducing signal. Thus, the Drosophila CNS midline cells play a central inductive role in patterning the mesoderm as well as the underlying ectoderm.

REFERENCES

Anderson
K.V.
(
1987
)
Dorsal-ventral embryonic pattern genes of Drosophila.
Trends Genet
3
,
91
97
Azpiazu
N.
,
Frasch
M.
(
1993
)
tinman and bagpipe: two homeobox genes that determine cell fates in the dorsal mesoderm of Drosophila.
Genes Dev
7
,
1325
1340
Azpiazu
N.
,
Lawrence
P. A.
,
Vincent
J.-P.
,
Frasch
M.
(
1996
)
Segmentation and specification of Drosophila mesoderm.
Genes & Development
10
,
3183
3194
Baker
R.
,
Schubiger
G.
(
1995
)
Ectoderm induces muscle-specific gene expression in Drosophila embryos.
Development
121
,
1387
1398
Baylies
M.K.
,
Bate
M.
(
1996
)
twist: A myogenic switch in Drosophila.
Science
272
,
1481
1484
Baylies
M.K.
,
Martinez Arias
A.
,
Bate
M.
(
1995
)
Wingless is required for the formation of a subset of muscle founder cells during Drosophila embryogenesis.
Development
121
,
3829
3837
Bieber
A.J.
,
Snow
P.M.
,
Hortsch
M.
,
Patel
N.H.
,
Jacobs
J.R.
,
Traquina
Z.R.
,
Schilling
J.
,
Goodman
C.S.
(
1989
)
Drosophila neuroglian: a member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1.
Cell
59
,
447
460
Bodmer
R.
,
Jan
L.Y.
,
Jan
Y.N.
(
1990
)
A new homeobox-containing gene, msh −2, is transiently expressed early during mesoderm formation of Drosophila.
Development
110
,
661
669
Bossing
T.
,
Technau
G. M.
(
1994
)
The fate of the CNS midline progenitors in Drosophila as revealed by a new method for single cell labelling.
Development
120
,
1895
1906
Bossing
T.
,
Udolph
G.
,
Doe
C.Q.
,
Technau
G.M.
(
1996
)
The embryonic CNS lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm.
Dev. Biol
179
,
41
61
Brand
A.H.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
Chiang
C.
,
Patel
N.H.
,
Young
K.E.
,
Beachy
P.A.
(
1994
)
The novel homeodomain gene buttonless specifies differentiation and axonal guidance functions of Drosophila dorsal median cells.
Development
120
,
3581
3593
Crews
S. T.
,
Thomas
J. B.
,
Goodman
C. S.
(
1988
)
The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product.
Cell
52
,
143
151
Dunin-Borkowski
O.M.
,
Brown
N.H.
,
Bate
M.
(
1995
)
Anterior-posterior subdivision and the diversification of the mesoderm in Drosophila.
Development
121
,
4183
4193
Finkelstein
R.
,
Smouse
D.
,
Capaci
T.M.
,
Spradling
A.C.
,
Perrimon
N.
(
1990
)
The orthodenticle gene encodes a novel homeodomain protein involved in the development of the Drosophila nervous system and ocellar visual structures.
Genes Dev
4
,
1516
1527
Frasch
M.
(
1995
)
Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo.
Nature
374
,
464
467
Freeman
M.
(
1996
)
Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye.
Cell
87
,
651
660
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
Golembo
M.
,
Raz
E.
,
Shilo
B.Z.
(
1996
)
The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm.
Development
122
,
3363
3370
Phillis
R.W.
,
Budnik
V.
(
1994
)
The role of tinman, a mesodermal cell fate gene, in axon pathfinding during the development of the transverse nerve in Drosophila.
Development
120
,
2143
2152
Govind
S.
,
Steward
R.
(
1991
)
Dorsoventral pattern formation.
Trends Genet
7
,
119
125
Hartenstein
A.
,
Rugendorf
A.
,
Tepass
U.
,
Hartenstein
V.
(
1992
)
The function of the neurogenic genes during epithelial development in the Drosophila embryo.
Development
116
,
1203
1220
Hilliker
A. J.
,
Clark
S.H.
,
Chovnick
A.
,
Gelbart
W.M.
(
1980
)
Cytogenetic analysis of the chromosomal region immediately adjacent to the rosy locus in Drosophila melanogaster.
Genetics
95
,
95
110
Hynes
M.
,
Poulsen
K.
,
Tessier-Lavigne
M.
,
Rosenthal
A.
(
1995
)
Control of neuronal diversity by the floor plate: contact mediated induction of midbrain dopaminergic neurons.
Cell
80
,
95
101
Kim
S.H.
,
Crews
S. T.
(
1993
)
Influence of Drosophila ventral epidermal development by the CNS midline cells and spitz class genes.
Development
118
,
893
901
Kingsbury
B.F.
(
1930
)
The developmental significance of the floor plate of the brain and spinal cord.
J. Comp. Neurol
50
,
177
207
Klaes
A.
,
Menne
T.
,
Stollewerk
A.
,
Scholz
H.
,
Klämbt
C.
(
1994
)
The ETS transcription factors encoded by the Drosophila gene pointed direct glial cell differentiation in the embryonic CNS.
Cell
78
,
149
160
Klämbt
C.
(
1993
)
The Drosophila gene pointed encodes two ets like proteins, which are involved in the development of the midline glial cells.
Development
117
,
163
176
Klämbt
C.
,
Goodman
C.S.
(
1991
)
The diversity and pattern of glia during axon pathway formation in the Drosophila embryo.
Glia
4
,
205
213
Klämbt
C.
,
Jacobs
J.R.
,
Goodman
C.S.
(
1991
)
The midline of the Drosophila central nervous system: a model for the genetic analysis of cell fate, cell migration, and growth cone guidance.
Cell
64
,
801
815
Kolodkin
A.L.
,
Pickup
A.T.
,
Lin
D. M.
,
Goodman
C.S.
,
Banerjee
U.
(
1994
)
Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor development in Drosophila.
Development
120
,
1731
1745
Kosman
D.
,
Ip
Y.T.
,
Levine
M.
,
Arora
K.
(
1991
)
Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo.
Science
254
,
118
122
Lehner
C.
,
O'Farell
P.H.
(
1989
)
Expression and function of Drosophila cyclin A during embryonic cell cycle progression.
Cell
56
,
957
968
Leptin
M.
(
1991
)
twist and snail as positive and negative regulators during Drosophila mesoderm development.
Genes Dev
5
,
1568
1576
Lewis
J.O.
,
Crews
S.T.
(
1994
)
Genetic analysis of the Drosophilasingle-minded gene reveals a central nervous system influence on muscle development.
Mech. Dev
48
,
81
91
Marshall
C.J.
(
1995
)
Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
Cell
80
,
179
185
Montell
D.J.
,
Goodman
C.S.
(
1989
)
Drosophila laminin: sequence of B2 subunit and expression of all three subunits during embryogenesis.
J. Cell Biol
109
,
2441
2453
Munsterberg
A. E.
,
Lassar
A. B.
(
1995
)
Combinatorial signals from the neural tube, floor plate and notochord induce myogenic bHLH gene expression in the somite.
Development
121
,
651
660
Murray
M.A.
,
Fessler
L.I.
,
Palka
J.
(
1995
)
Changing distributions of extracellular matrix components during early wing morphogenesis in Drosophila.
Dev. Biol
168
,
150
165
Nambu
J. R.
,
Lewis
J. O.
,
Wharton
K. A.
,
Crews
S. T.
(
1991
)
The Drosophilasingle-minded gene encodes a helix-loop-helix protein that acts as a master regulator of midline development.
Cell
67
,
1157
1167
Okabe
M.
,
Sawamoto
K.
,
Okano
H.
(
1996
)
The function of the Drosophilaargos gene product in the development of embryonic chordotonal organs.
Dev. Biol
175
,
37
49
Olson
P.F.
,
Fessler
L.I.
,
Nelson
R.E.
,
Sterne
R.
,
Campbell
A.G.
,
Fessler
J.H.
(
1990
)
Glutactin, a novel Drosophila basement membrane-related glycoprotein with sequence similarity to serine esterases.
EMBO J
9
,
1219
1227
Osborne
M.P.
(
1964
)
The structure of the unpaired ventral nerves in the blowfly larva.
Quart. J. Micr. Sci
105
,
325
329
Pourquie
O.
,
Fan
C. M.
,
Coltey
M.
,
Hirsinger
E.
,
Watanabe
Y.
,
Breant
C.
,
Francis-West
P.
,
Brickell
P.
,
Tessier-Lavigne
M.
,
Le Douarin
N. M.
(
1996
)
Lateral and axial signals involved in avian somite patterning: a role for BMP4.
Cell
84
,
461
471
Ranganayakulu
G.
,
Schulz
R.A.
,
Olson
E.N.
(
1996
)
Wingless signaling induces nautilus expression in the ventral mesoderm of the Drosophila embryo.
Dev. Biol
176
,
143
148
Raz
E.
,
Shilo
B.-Z.
(
1993
)
Establishment of ventral fates in the Drosophila embryonic ectoderm requires DER, the EGF receptor homolog.
Genes Dev
7
,
193
1948
Roth
S.
,
Stein
D.
,
Nusslein-Volhard
C.
(
1989
)
A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo.
Cell
59
,
1189
1202
Rushlow
D.A.
,
Arora
K.
(
1990
)
Dorsal ventral polarity and pattern formation in the Drosophila embryo.
Semin. Cell Biol
1
,
137
149
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
Schmidt-Ott
U.
,
Technau
G.M.
(
1992
)
Expression of en and wg in the embryonic head and brain of Drosophila indicates a refolded band of seven segment remnants.
Development
116
,
111
125
Schneider
L.E.
,
O'Brien
M.A.
,
Taghert
P.H.
(
1991
)
In situ hybridization analysis of the FMRFamide neuropeptide gene in Drosophila. Part I. Restricted expression in embryonic and larval stages.
J. Comp. Neurol
304
,
608
622
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.
,
Shahrabany
M.
,
Seger
R.
,
Shilo
B.-Z.
(
1995
)
Secreted spitz triggers the DER signaling pathway and is a limiting component in the embryonic ventral ectoderm determination.
Genes Dev
9
,
1518
11529
Schweitzer
R.
,
Howes
R.
,
Smith
R.
,
Shilo
B.-Z.
,
Freeman
M.
(
1995
)
Inhibition of Drosophila EGF receptor activation by the secreted protein Argos.
Nature
376
,
699
702
Sonnenfeld
M.J.
,
Jacobs
J.R.
(
1994
)
Mesectodermal cell fate analysis in Drosophila midline mutants.
Mech. Dev
46
,
3
13
Staehling-Hampton
K.
,
Hoffmann
F.M.
,
Baylies
M.K.
,
Rushton
E.
,
Bate
M.
(
1994
)
dpp induces mesodermal gene expression in Drosophila.
Nature
372
,
783
786
St. Johnston
R.D.
,
Nusslein-Volhard
(
1992
)
The origin of pattern and polarity in the Drosophila embryo.
Cell
68
,
201
219
Sturtevant
M.A.
,
Roark
M.
,
O'Neill
J.W.
,
Biehs
B.
,
Colley
N.
,
Bier
E.
(
1996
)
The Drosophilarhomboid protein is concentrated in patches at the apical cell surface.
Dev. Biol
174
,
298
309
Thisse
B.
,
Stoetzel
C.
,
Perrin-Schmidt
M.
(
1987
)
Genes of the Drosophila maternal dorsal group control the specific expression of the zygotic gene twist in presumptive mesodermal cells.
Genes Dev
1
,
709
715
Thomas
J.B.
,
Crews
S.T.
,
Goodman
C.S.
(
1988
)
Molecular genetics of the single-minded locus: a gene involved in the development of the Drosophila nervous system.
Cell
52
,
133
141
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
White
K.
,
Hurteau
T.
,
Punsal
P.
(
1986
)
Neuropeptide-FMRFamide-like immunoreactivity in Drosophila: Distribution and development.
J. comp. Neurol
247
,
430
438
Xu
T.
,
Rubin
G.M.
(
1993
)
Analysis of genetic mosaics in developing and adult Drosophila tissues.
Development
117
,
1223
1237
Yamada
T.
,
Pfaff
S.
,
Edlund
T.
,
Jessell
T.M.
(
1993
)
Control of cell pattern in the neural tube: Motorneuron induction by diffusible factors from the notochord and floor plate.
Cell
73
,
673
686
Zitnan
D.
,
Sehnal
F.
,
Bryant
P.J.
(
1993
)
Neurons producing specific neuropeptides in the central nervous system of normal and pupariation-delayed Drosophila.
Dev. Biol
156
,
117
135
This content is only available via PDF.