Glial-neuronal cell interactions at the ventral midline are necessary for the proper elaboration of commissures in the embryonic CNS of Drosophila. In particular, migrating midline glial cells are required for the separation of segmental commissures. During this process the glial cells recognize specific neuronal cells at the midline, they migrate posteriorly along their cell processes and thereby separate the segmental commissures. The gene pointed (pnt) is required for this glial-neuronal cell interaction, as loss of function mutations lead to a change in the migration behavior of the midline glial cells. As a consequence, anterior and posterior commissures do not become separated and appear fused. Molecular analysis of pointed has revealed two differently spliced types of transcripts, which are encoded in a region extending over 55 kb of genomic sequence. In the CNS both transcript classes are expressed in cells of the midline, including the midline glial cells. Sequence analysis of cDNA clones corresponding to both transcript types reveals two different pointed proteins which share an ETS domain common to a number of transcription factors related to the vertebrate ets oncogene. Furthermore, one pointed protein form contains an additional domain of homology of approx. 80 amino acids in length, which is shared by only a subset of the ETS protein family.

REFERENCES

Anton
J. A.
,
Frampton
J.
(
1988
)
Tryptophans in myb proteins.
Nature
336
,
719
–.
Bastiani
M. J.
,
Goodman
C. S.
(
1986
)
Guidance of neuronal growth cones in the grasshopper embryo. III. Recognition of specific glial pathways.
J. Neurosci
6
,
3542
3551
Bate
M.
(
1990
)
The embryonic development of larval muscles in Drosophila.
Development
110
,
791
802
Ben-David
Y.
,
Giddens
E. B.
,
Letwin
K.
,
Bernstein
A.
(
1991
)
Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1.
Genes Dev
5
,
908
918
Bier
E.
,
Jan
L. Y.
,
Jan
Y. N.
(
1990
)
rhomboid, a gene required for dorso-ventral axis establishment and peripheral nervous system development in Drosophila melanogaster.
Genes Dev
4
,
190
203
Billin
A. N.
,
Cockerill
K. A.
,
Poole
S. J.
(
1991
)
Isolation of a family of Drosophila POU domain genes expressed in early development.
Mech. Dev
34
,
75
84
Boloventa
P.
,
Dodd
J.
(
1990
)
Guidance of commissural growth cones at the floor plate in the embryonic rat spinal cord.
Development
109
,
625
639
Burtis
K. C.
,
Thummel
C. S.
,
Jones
C. W.
,
Karim
F. D.
,
Hogness
D. S.
(
1990
)
The Drosophila 74EF early puff contains E74, a complex ecdyson-inducible gene that encodes two ets related proteins.
Cell
61
,
85
99
Cavener
D.
(
1987
)
Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates.
Nucl. Acid. Res
15
,
1353
1361
Chen
T.
,
Bunting
M.
,
Karim
F. D.
,
Thummel
C. S.
(
1992
)
Isolation and characterization of five Drosophila genes that encode an ets related DNA binding domain.
Dev. Biol
151
,
176
191
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
Dodd
J.
,
Jessel
T. M.
(
1988
)
Axon guidance and the patterning of neuronal projections in vertebrates.
Science
242
,
692
699
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
Foe
V. E.
(
1989
)
Mitotic domains reveal early commitment of cells in Drosophila embryos.
Development
107
,
1
22
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
Fujita
C. S.
,
Zirpursky
S. L.
,
Benzer
S.
,
Ferrus
A.
,
Shotwell
S. L.
(
1982
)
Monoclonal antibodies against the Drosophila nervous system.
Proc. Natl. Acad. Sci. USA
79
,
59
69
Gunther
C. V.
,
Nye
J. A.
,
Bryner
R. S.
,
Graves
B. J.
(
1990
)
Sequence-specific DNA binding of the protooncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus.
Genes Dev
4
,
667
679
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
Jacobs
J. R.
,
Goodman
C. S.
(
1989
)
Embryonic development of axon pathways in the Drosophila CNS: II. Behavior of pioneer growth cones.
J. Neurosci
9
,
2412
2422
Jacobs
J. R.
,
Hiromi
Y.
,
Patel
N. H.
,
Goodman
C. S.
(
1989
)
Lineage, migration and morphogenesis of longitudinal glia in the Drosophila CNS as revealed by a molecular lineage marker.
Neuron
2
,
1625
1631
Johnson
W.
,
Hirsh
J.
(
1990
)
Binding of a Drosophila POU-domain protein to a sequence element regulating gene expression in specific dopaminergic neurons.
Nature
343
,
467
470
Karim
F. D.
,
Urness
L. D.
,
Thummel
C. S.
,
Klemsz
M. J.
,
McKercher
S. R.
,
Celada
A.
,
van Beveren
C.
,
Maki
R. A.
,
Gunther
C. V.
,
Nye
J. A.
,
Graves
B. J.
(
1990
)
The ETS-domain: a new DNA binding motif that recognizes a purine rich core DNA sequence.
Genes Dev
4
,
1451
1453
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
R. J.
,
Goodman
C. S.
(
1991
)
The midline of the Drosophila CNS: Model and genetic analysis of cell lineage, cell migration, and development of commissural axon pathways.
Cell
64
,
801
815
Klämbt
C.
,
Glaser
L.
,
Shilo
B.-Z.
(
1992
)
breathless, a Drosophila FGF receptor homolog, is essential for the migration of tracheal and specific midline glial cells.
Genes Dev
6
,
1668
1678
Kosman
D.
,
Ip
Y. T.
,
Levine
M.
,
Arora
K.
(
1991
)
Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo.
Science
254
,
118
122
Kretzschmar
D.
,
Brunner
A.
,
Wiersdorff
V.
,
Pflugfelder
G. O.
,
Heisenberg
M.
,
Schneuwly
S.
(
1992
)
giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster.
EMBO J
11
,
2531
2539
LaMarco
K.
,
Thompson
C. C.
,
Byers
B. P.
,
Walton
E. M.
,
McKnight
S. L.
(
1991
)
Identification of ets and Notch related subunits in GA binding protein.
Science
253
,
789
792
Leptin
M.
(
1991
)
twist and snail as positive and negative regulators during Drosophila mesoderm development.
Genes Dev
5
,
1568
1576
Mayer
U.
,
Nusslein-Volhard
C.
(
1988
)
A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo.
Genes Dev
2
,
1496
1511
Nambu
J. R.
,
Franks
R. G.
,
Hu
S.
,
Crews
S. T.
(
1990
)
The single-minded gene of Drosophila is required for the expression of genes important for the development of CNS midline cells.
Cell.
63
,
63
75
Nambu
J. R.
,
Lewis
J. O.
,
Wharton
K. A.
,
Crews
S. T.
(
1991
)
The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of midline development.
Cell
67
,
1157
1167
Pearson
W. R.
,
Lipman
D. J.
(
1988
)
Improved tools for biological sequence comparison.
Proc. Natl. Acad. Sci. USA
85
,
2444
2448
Placzek
M.
,
Tessier-Levigne
M.
,
Jessel
T. M.
,
Dodd
J.
(
1990
)
Orientation of commissural axons in vitro in response to a floor plate derived chemoattractant.
Development
110
,
19
30
Pribyl
L. J.
,
Watson
D. K.
,
McWilliams
M. J.
,
Ascione
R.
,
Papas
T. S.
(
1988
)
The Drosophila ets2 gene: molecular structure, chromosomal location and developmental expression.
Dev. Biol
127
,
45
53
Pribyl
L. J.
,
Watson
D. K.
,
Schulz
R. A.
,
Papas
T. S.
(
1991
)
D- elg, a member of the Drosophilaets gene family: a sequence, expression and evolutionary comparison.
Oncogene
6
,
1175
1183
Reddy
E. S. P.
,
Rao
V. N.
,
Papas
T. S.
(
1987
)
The erg gene: a human gene related to the ets oncogene.
Proc. Natl. Acad. Sci. USA
84
,
6131
6135
Rao
V. N.
,
Huebner
K.
,
Isobe
M.
,
Ar-Rushdi
A.
,
Croce
C. M.
,
Reddy
E. S. P.
(
1989
)
elk, tissue specific ets related genes on chromosomes X and 14 near translocation breakpoints.
Science
244
,
66
70
Raz
E.
,
Shilo
B.-Z.
(
1992
)
Dissection of the faint little ball (flb) phenotype: Determination of the development of the Drosophila central nervous system by early interactions in the ectoderm.
Development
114
,
113
123
Robertson
H. M.
,
Preston
C. R.
,
Phillis
R. W.
,
Johnson-Schlitz
D. M.
,
Benz
W. K.
,
Engels
W. R.
(
1988
)
A stable source of P-element transposase in Drosophila melanogaster.
Genetics
118
,
6341
6351
Rothberg
J. M.
,
Hartley
D. A.
,
Walther
Z.
,
Artavanis-Tsakonas
S.
(
1988
)
slit: an EGF-homologous locus in Drosophila melanogaster involved in the development of the embryonic central nervous system.
Cell
55
,
1047
1059
Rothberg
J. M.
,
Jacobs
J. R.
,
Goodman
C. S.
,
Artavanis-Tsakonas
S.
(
1990
)
slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains.
Genes Dev
4
,
2169
2187
Rutledge
B. J.
,
Zhang
K.
,
Bier
E.
,
Jan
Y. N.
,
Perrimon
N.
(
1992
)
The Drosophila gene spitz encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis.
Genes Dev
6
,
1503
1517
Schneikert
J.
,
Lutz
Y.
,
Wasylyk
B.
(
1992
)
Two conserved activation domains in c-Ets-1 ans c-Ets-2 located in nonconserved sequences of the ets gene family.
Oncogene
7
,
249
256
Stitt
T. N.
,
Hatten
M. E.
(
1990
)
Antibodies that recognize astrotactin block granule neuron binding to astroglia.
Neuron
5
,
639
649
Sink
H.
,
Whitington
P.
(
1991
)
Location and connectivity of abdominal motorneurons in the embryo and larva of Drosophila melanogaster.
J. Neurobiol
22
,
298
311
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
Tepass
U.
,
Theres
C.
,
Knust
E.
(
1990
)
crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia.
Cell
61
,
787
799
Tessier-Lavigne
M.
,
Placzek
M.
,
Lumsden
A.
,
Dodd
J.
,
Jessell
T.
(
1988
)
Chemotropic guidance of developing axons in the mammalian central nervous system.
Nature
336
,
775
778
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
Watson
D. K.
,
McWilliams
M. J.
,
Lapis
P.
,
Lautenberger
J. A.
,
Schweinfest
C. W.
,
Papas
T. S.
(
1988
)
Mammalian ets-1 and ets-2 genes encode highly conserved proteins.
Proc. Natl. Acad. Sci. USA
85
,
7862
7866
Watson
D. K.
,
McWilliams
M. J.
,
Papas
T. S.
(
1988
)
Molecular organization of the chicken ets locus.
Virology
164
,
99
105
Zak
N. B.
,
Wides
R. J.
,
Schejter
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
Zinn
K.
,
McAllister
L.
,
Goodman
C. S.
(
1988
)
Sequence analysisand neuronal expression of fasciclin I in grasshopper and Drosophila.
Cell
53
,
577
587
Xin
J.-H.
,
Cowie
A.
,
Lachance
P.
,
Hassell
J. A.
(
1992
)
Molecular cloning and characterization of PEA3, a new member of the ets oncogene family that is differentially expressed in mouse embryonic cells.
Genes Dev
66
,
481
496
This content is only available via PDF.