Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.

Alberga
A.
,
Boulay
J.-L.
,
Kempe
E.
,
Dennefeld
C.
,
Haenlin
M.
(
1991
)
The snail gene required for mesoderm formation in Drosophila is expressed dynamically in derivatives of all three germ layers.
Development
111
,
983
992
Anderson
D. J.
(
1995
)
A molecular switch for the neuron-glia development decision.
Neuron
15
,
1219
1222
Bardwell
V. J.
,
Treisman
R.
(
1994
)
The POZ domain: A conserved protein-protein interaction motif.
Genes Dev
8
,
1664
1677
Bossing
T.
,
Technau
G. M.
(
1994
)
The fate of the CNS midline progenitors in Drosophila as revealed by a new method for single cell labeling.
Development
120
,
1895
1906
Brand
A. H.
,
Perrimon
N.
(
1993
)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Development
118
,
401
415
Brown
J. L.
,
Sonoda
S.
,
Ueda
H.
,
Scott
M.
,
Wu
C.
(
1991
)
Repression of the Drosophila fushi tarazu (ftz) segmentation gene.
EMBO J
10
,
665
674
Brown
J. L.
,
Wu
C.
(
1993
)
Repression of Drosophila pair-rule segmentation genes by ectopic expression of tramtrack.
Development
117
,
45
58
Brunner
D.
,
Ducker
K.
,
Oellers
N.
,
Hafen
E.
,
Scholz
H.
,
Klämbt
C.
(
1994
)
The ETS domain protein PointedP1 is a target of MAP kinase in the Sevenless signaling pathway.
Nature
370
,
386
389
Campbell
G.
,
Göring
H.
,
Lin
T.
,
Spana
E.
,
Andersson
S.
,
Doe
C. Q.
,
Tomlinson
A.
(
1994
)
RK2, a glial-specific homeodomain protein required for embryonic nerve cord condensation and viability in Drosophila.
Development
120
,
2957
2966
Carlson
S. D.
,
Saint Marie
R. L.
(
1990
)
Structure and function of insect glia.
Annu. Rev. Entomol
35
,
597
621
Carthew
R. W.
,
Rubin
G. M.
(
1990
)
seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eye.
Cell
63
,
561
577
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
Chong
J. A.
,
Tapia-Ramirez
J.
,
Kim
S.
,
Toledo-Aral
J. J.
,
Zheng
Y.
,
Boutros
M. C.
,
Altshuller
Y. M.
,
Frohman
M. A.
,
Kraner
S. D.
,
Mandel
G.
(
1995
)
REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons.
Cell
80
,
949
957
Condron
B. G.
,
Zinn
K.
(
1994
)
The grasshopper median neuroblast is a multipotent progenitor cell that generates glia and neurons in distinct temporal phases.
J Neurosci
14
,
5766
5777
Doe
C. Q.
,
Chu-LaGraff
Q.
,
Wright
D. M.
,
Scott
M. P.
(
1991
)
The prospero gene specifies cell fates in the Drosophila central nervous system.
Cell
65
,
451
464
Ebens
A. J.
,
Garren
H.
,
Cheyette
B. N.
,
Zipursky
S. L.
(
1993
)
The Drosophila anachronism locus: a glycoprotein secreted by glia inhibits neuroblast proliferation.
Cell
74
,
15
27
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
Gorczyca
M. G.
,
Phillis
R. W.
,
Budnik
V.
(
1994
)
The role of tinman, a mesodermal cell fate gene during the development of the transverse nerve in Drosophila.
Development
120
,
2143
2152
Grenningloh
G.
,
Rehm
E. J.
,
Goodman
C. S.
(
1991
)
Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule.
Cell
67
,
45
57
Guo
M.
,
Bier
E.
,
Jan
L.
,
Jan
Y. N.
(
1995
)
tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS.
Neuron
14
,
913
925
Halter
D. A.
,
Urban
J.
,
Rickert
C.
,
Ner
S. S.
,
Ito
K.
,
Travers
A.
,
Technau
G. M.
(
1995
)
The homeobox gene repo is required for the differentiation and maintenance of glia function in the embryonic nervous system of Drosophilamelanogster.
Development
121
,
317
332
Harrison
S.
,
Travers
A.
(
1990
)
The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern.
EMBO J
9
,
207
216
Hosoya
T.
,
Takizawa
K.
,
Nitta
K.
,
Hotta
Y.
(
1995
)
glial cells missing: a binary switch between neuronal and glial determination in Drosophila.
Cell
82
,
1025
1036
Hoyle
G.
(
1986
)
Glial cells of an insect ganglion.
J. of Comp. Neurology
246
,
85
103
Jacobs
J. R.
(
1993
)
Perturbed glial scaffold formation precedes axon tract malformation in Drosophila mutants.
J. of Neurobiol
24
,
611
626
Jacobs
J. R.
,
Goodman
C. S.
(
1989
)
Embryonic development of axon pathways in the Drosophila CNS: I. A glial scaffold appears before the first growth cones.
J. Neurosci
9
,
2402
2411
Jones
B. W.
,
Fetter
R. J.
,
Tear
G.
,
Goodman
C. S. G.
(
1995
)
glial cells missing: a genetic switch that controls glial versus neuronal fate.
Cell
82
,
1013
1023
Karpen
G.
,
Spradling
A. C.
(
1992
)
Analysis of subtelomeric heterochromatin in the Drosophila minichromosome Dp1187 by single P element insertional analysis.
Genetics
132
,
737
753
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.
,
Hummel
T.
,
Menne
T.
,
Sadlowski
S.H.S.A.S.
(
1996
)
Development and function of embryonic CNS glial cells in Drosophila.
Developmental Genetics
18
,
40
49
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.
,
Jacobs
R. J.
,
Goodman
C. S.
(
1991
)
The midline of the Drosophila CNS: Model and genetic analysis of cell lineage, cell migration, development of commissural axon pathways.
Cell
64
,
801
815
Labouesse
M.
,
Hartwieg
E.
,
Horvitz
H. R.
(
1996
)
The Caenorhabditis elegans lin-26 protein is required to specify and/or maintain all non-neuronal ectodermal cell fates.
Development
122
,
2579
2588
Lai
Z. C.
,
Harrison
S. D.
,
Karim
F.
,
Li
Y.
,
Rubin
G. M.
(
1996
)
Loss of tramtrack gene activity results in ectopic R7 cell formation, even in a sina mutant background.
Proc. Natl. Acad. Sci. USA
93
,
5025
5030
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
Raz
E.
,
Shilo
B.-Z.
(
1992
)
Dissection of the faintlittleball (flb) phenotype: Determination of the development of the Drosophila central nervous system by early interactions in the ectoderm.
Development
114
,
113
123
Read
D.
,
Levine
M.
,
Manley
J. L.
(
1992
)
Ectopic expression of the Drosophilatramtrack gene results in multiple embryonic defects, including repression of even-skipped and fushi tarazu.
Mech. Dev
38
,
183
195
Read
D.
,
Manley
J.
(
1992
)
Alternatively spliced transcripts of the Drosophilatramtrack gene encode zinc finger proteins with distinct DNA binding properties.
EMBO J
11
,
1035
1044
Robinow
S.
,
White
K.
(
1988
)
The locus elav of Drosophila melanogaster is expressed in neurons at all developmental stages.
Dev. Biol
126
,
294
303
Salzberg
E.
,
D'Evelyn
D.
,
Schultze
K.
,
Lee
J.-K.
,
Strumpf
D.
,
Tsai
L.
,
Bellen
H. J.
(
1994
)
Mutations affecting the pattern of the PNS in Drosophila reveal novel aspects of neuronal development.
Neuron
13
,
269
287
Schoenherr
C. J.
,
Anderson
D. J.
(
1995
)
The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes.
Science
267
,
1360
1363
Scholz
H.
,
Deatrick
J.
,
Klaes
A.
,
Klämbt
C.
(
1993
)
Genetic dissection of pointed, a Drosophila gene encoding two ets related proteins.
Genetics
135
,
455
468
Scholz
H.
,
Sadlowski
E.
,
Klaes
A.
,
Klämbt
C.
(
1997
)
Control of midline glia development in the embryonic Drosophila CNS.
Mech. Dev
62
,
79
91
Seto
E.
,
Shi
Y.
,
Shenk
T.
(
1991
)
YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro.
Nature
354
,
241
245
Shi
Y.
,
Seto
E.
,
Chang
L. S.
,
Shenk
T.
(
1991
)
Transcriptional repression by YY1, a human GLI-Kruppel-related protein, and relief of repression by adenovirus E1A protein.
Cell
67
,
377
388
Soula
C.
,
Foulquier
F.
,
Duprat
A. M.
,
Cochard
P.
(
1993
)
Lineage analysis of early neural plate cells: cells with purely neuronal fate coexist with bipotential neuroglial progenitors.
Dev. Biol
159
,
196
207
Stollewerk
A.
,
Klämbt
C.
,
Cantera
R.
(
1996
)
Electronmicroscopic analysis of midline glial cell development during embryogenesis and larval development using-galactosidase expression as endogenous cell marker.
Microscopy Research and Technique
35
,
294
306
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
Vincent
S.
,
Vonesch
J.-L.
,
Giangrande
A.
(
1996
)
glide directs glial fate commitment and cell fate switch between neurones and glia.
Development
122
,
131
139
Xiong
W.-C.
,
Okano
H.
,
Patel
N. P.
,
Montell
C.
(
1994
)
repo encodes a glial-specific homeo domain protein required in the Drosophila nervous system.
Genes Dev
8
,
981
994
Xiong
W. C.
,
Montell
C.
(
1995
)
Defective glia induce neuronal apoptosis in the repo visual system of Drosophila.
Neuron
14
,
581
590
Xiong
W. C.
,
Montell
C.
(
1993
)
tramtrack is a transcriptional repressor required for cell fate determination in the Drosophila eye.
Genes Dev
7
,
1085
1096
Zak
N. B.
,
Wides
R. J. S. E.D.
,
Raz
E.
,
Shilo
B.-Z.
(
1990
)
Localization of the DER/flb protein in embryos: implications on the faint little ball lethal phenotype.
Development
109
,
865
874
Zipursky
S. L.
,
Rubin
G. M.
(
1994
)
Determination of neuronal cell fate: lessons from the R7 neuron of Drosophila.
Ann. Rev. Neurosci
17
,
373
397
Zollman
S.
,
Godt
D.
,
Prive
G. G.
,
Couderc
J. L.
,
Laski
F. A.
(
1994
)
The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila.
Proc. Natl. Acad. Sci.USA
91
,
10717
10721
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