Mutations in the gene longitudinals lacking (lola) lead to defects in the development of axon tracts in the Drosophila embryonic central nervous system. We now show that lola mutations also cause defects of axon growth and guidance in the peripheral nervous system, and causes a particular cluster of embryonic sense organs (lch5) to be oriented improperly. Axonal aberrations caused by lola are similar to those caused by mutations of three other genes, logo, Notch and Delta, raising the possibility that lola works in the same genetic pathway as do these other molecules. The lola gene encodes at least two nuclear protein products, apparently by differential RNA splicing. The predicted proteins contain an amino-terminal motif similar to that recently described for a family of transcription factors, including the products of the Drosophila genes tramtrack and the Broad Complex. Like Ttk and BR-C, one of the two characterized products of the lola locus bears sequences similar to the zinc-finger motif, but the other (neuronal) form of the protein has no recognizable DNA-binding motif.
REFERENCES
Anderson
K. V.
, Nusslein-Volhard
C.
(1984
) Information for the dorsal-ventral pattern of the Drosophila embryo is stored as maternal RNA.
Nature
311
, 223
–227
Bier
E.
, Ackerman
L.
, Barbel
S.
, Jan
L.
, Jan
Y. N.
(1988
) Identification and characterization of a neuron-specific antigen in Drosophila.
Science
240
, 913
–916
Bier
E.
, Vaessin
H.
, Shepherd
S.
, Lee
K.
, McCall
K.
, Barbel
S.
, Ackerman
L.
, Carretto
R.
, Uemura
T.
, Grell
E.
, Jan
L. Y.
, Jan
Y. N.
(1989
) Searching for pattern and mutation in the Drosophila genome with a P- lacZ vector.
Genes Dev
3
, 1273
–87
Biggin
M. D.
, Tjian
R.
(1988
) Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts.
Cell
53
, 699
–711
Blochlinger
K.
, Bodmer
R.
, Jack
J.
, Jan
L. Y.
, Jan
Y. N.
(1988
) Primary structure and expression of a product from cut, a locus involved in specifying sensory organ identity in Drosophila.
Nature
333
, 629
–35
Blochlinger
K.
, Bodmer
R.
, Jan
L. Y.
, Jan
Y. N.
(1990
) Patterns ofexpression of Cut, a protein required for external sensory organ development in wild-type and cut mutant Drosophila embryos.
Genes Dev
4
, 1322
–1331
Boulay
J. L.
, Dennefeld
C.
, Alberga
A.
(1987
) The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers.
Nature
330
, 395
–8
Brown
J. L.
, Sonoda
S.
, Ueda
H.
, Scott
M. P.
, Wu
C.
(1991
) Repression of the Drosophilafushi tarazu (ftz) segmentation gene.
EMBO J
10
, 665
–74
Brown
J. L.
, Wu
C.
(1993
) Repression of Drosophila pair rule segmentation genes by ectopic expression of tramtrack.
Development
117
, 45
–58
Chardin
P.
, Courtois
G.
, Mattei
M. G.
, Gisselbrecht
S.
(1991
) The KUP gene, located on human chromosome 14, encodes a protein with two distant zinc fingers.
Nucleic Acids Res
19
, 431
–6
Chelsky
D.
, Ralph
R.
, Jonak
G.
(1989
) Sequence requirements for synthetic peptide-mediated translocation to the nucleus.
Mol. Cell. Biol
9
, 2487
–2492
Corbin
V.
, Michelson
A. M.
, Abmayr
S. M.
, Neel
V.
, Alcamp
E.
, Maniatis
T.
, Young
M. W.
(1991
) A role for the Drosophila neurogenic genes in mesoderm differentiation.
Cell
67
, 311
–323
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
–51
Devereux
J.
, Haeberli
P.
, Smithies
O.
(1984
) A comprehensive set of sequence analysis programs for the VAX.
Nucleic Acids Res
12
, 387
–395
DiBello
P. R.
, Withers
D. A.
, Bayer
C. A.
, Fristrom
J. W.
, Guild
G. M.
(1991
) The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers.
Genetics
129
, 385
–97
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
–164
Doe
C. Q.
, Hiromi
Y.
, Gehring
W. J.
, Goodman
C. S.
(1988
) Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis.
Science
239
, 170
–175
Doe
C. Q.
, Smouse
D.
, Goodman
C. S.
(1988
) Control of neuronal fate by the Drosophila segmentation gene even-skipped.
Nature
333
, 376
–378
Foe
V. E.
(1989
) Mitotic domains reveal early commitment of cells in Drosophila embryos.
Development
107
, 1
–22
Gerster
T.
, Roeder
R. G.
(1988
) A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins.
Proc. Natl Acad. Sci. USA
85
, 6347
–51
Giniger
E.
, Jan
L. Y.
, Jan
Y. N.
(1993
) Specifying the path of the intersegmental nerve of the Drosophila embryo: a role for Delta and Notch.
Development
117
, 431
–440
Harrison
S. D.
, Travers
A. 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
–16
Hartenstein
A. Y.
, Hartenstein
V.
(1993
) The role of the tracheae and musculature during pathfinding of Drosophila embryonic sensory organs.
Dev. Biol
158
, 430
–447
Hartenstein
V.
(1988
) Development of Drosophila larval sensory organs: spatiotemporal pattern of sensory neurones, peripheral axonal pathways and sensilla differentiation.
Development
102
, 869
–886
Hartenstein
V.
, Posakony
J.
(1990
) A dual function of the Notch gene in Drosophila sensillum development.
Dev. Biol
142
, 13
–30
Ishii
N.
, Wadsworth
W. G.
, Stern
B. D.
, Culotti
J. G.
, Hedgecock
E. M.
(1992
) UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans.
Neuron
9
, 873
–881
Jan
L. Y.
, Jan
Y. N.
(1982
) Antibodies to horseradish peroxidase as specific neuronal markers in Drosophila and in grasshopper embryos.
Proc. Natl Acad. Sci. USA
72
, 2700
–2704
Karim
F. D.
, Guild
G. M.
, Thummel
C. S.
(1993
) The Drosophila Broad-Complex plays a key role in controlling ecdysone-regulated gene expression at the onset of metamorphosis.
Development
118
, 977
–988
Keleher
C. A.
, Redd
M. J.
, Schultz
J.
, Carlson
M.
, Johnson
A. D.
(1992
) Ssn6-Tup1 is a general repressor of transcription in yeast.
Cell
68
, 709
–719
Klambt
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
Koonin
E. V.
, Senkevich
T. G.
, Chernos
V. I.
(1992
) A family of DNA virus genes that consists of fused portions of unrelated cellular genes.
TIBS
17
Kristie
T. M.
, Sharp
P. A.
(1990
). Interactions of the Oct-1 POU subdomains with specific DNA sequences and with the HSV alpha-trans-activator protein.
Genes Dev
4
, 2383
–96
Leung-Hagesteijn
C.
, Spence
A. M.
, Stern
B. D.
, Zhou
Y.
, Su
M.-W.
, Culotti
J. G.
(1992
) UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1 domains, guides cell and pioneer axon migration in C. elegans.
Cell
71
, 289
–299
Matsuzaki
F.
, Koizumi
K.
, Hama
C.
, Yoshioka
T.
, Nabeshima
Y.
(1992
) Cloning of the Drosophilaprospero gene and its expression in ganglion mother cells.
Biochem. Biophys. Res. Commun
182
, 1326
–32
McIntire
S. L.
, Garriga
G.
, White
J.
, Jacobson
D.
, Horvitz
H. R.
(1992
) Genes necessary for directed axonal elongation or fasciculation in C. elegans.
Neuron
8
, 307
–322
Miller
J.
, McLachlan
A. D.
, Klug
A.
(1985
) Repetitive Zn-binding domains in the protein transcription factor IIIA from Xenopus oocytes.
EMBO J
4
, 1609
–1614
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 CNS midline development.
Cell
67
, 1157
–67
Nonet
M. L.
, Meyer
B. J.
(1991
) Early aspects of Caenorhabditis elegans sex determination and dosage compensation are regulated by a zinc-finger protein.
Nature
351
, 65
–8
Nusslein-Volhard
C.
, Frohnhofer
H. G.
, Lehmann
R.
(1987
) Determination of anteroposterior polarity in Drosophila.
Science
238
, 1675
–1681
Payre
F.
, Noselli
S.
, Lefrere
V.
, Vincent
A.
(1990
) The closely related Drosophila sry beta and sry delta zinc finger proteins show differential embryonic expression and distinct patterns of binding sites on polytene chromosomes.
Development
110
, 141
–9
Poole
S. J.
, Kauvar
L. M.
, Drees
B.
, Kornberg
T.
(1985
) The engrailed locus of Drosophila: Structural analysis of an embryonic transcript.
Cell
40
, 37
–43
Rao
Y.
, Jan
L. Y.
, Jan
Y. N.
(1990
) Similarity of the product of the Drosophila neurogenic gene big brain to transmembrane channel proteins.
Nature
345
, 163
–7
Robertson
H. M.
, Preson
C. R.
, Phillis
R. W.
, Johnson-Schlitz
D.
, Benz
W. K.
, Engels
D. R.
(1988
) A stable source of P-element transposase in Drosophilamelanogaster.
Genetics
118
, 461
–470
Ruther
U.
, Muller-Hill
B.
(1983
) Easy identification of cDNA clones.
EMBO J
2
, 1791
–1794
Sargent
M. G.
, Bennett
M. F.
(1990
) Identification in Xenopus of a structural homologue of the Drosophila gene snail.
Development
109
, 967
–73
Seeger
M.
, Tear
G.
, Ferres-Marco
D.
, Goodman
C. S.
(1993
) Mutations affecting growth cone guidance in Drosophila: Genes necessary for guidance towards or away from the midline.
Neuron
10
, 409
–426
Soeller
W. C.
, Oh
C. E.
, Kornberg
T. B.
(1993
) Isolation of cDNAs encoding the Drosophila GAGA transcription factor.
Mol. Cell. Biol
13
, 7961
–7970
Stern
S.
, Herr
W.
(1991
) The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeodomain: evidence for a homeo domain recognition subdomain.
Genes Dev
5
, 2555
–66
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
Vaessin
H.
, Grell
E.
, Wolff
E.
, Bier
E.
, Jan
L. Y.
, Jan
Y. N.
(1991
) prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila.
Cell
67
, 941
–53
Whiteley
M.
, Noguchi
P. D.
, Sensabaugh
S. M.
, Odenwald
W. F.
, Kassis
J. A.
(1992
) The Drosophila gene escargot encodes a zinc finger motif found in snail -related genes.
Mech. Dev
36
, 117
–27
Xiong
W.-C.
, Montell
C.
(1993
) Tramtrack is a trancriptional repressor required for cell fate determination in the Drosophila eye.
Genes Dev
7
, 1085
–1096
Xue
F.
, Cooley
L.
(1993
) kelch encodes a component of intercellular bridges in Drosophila egg chanbers.
Cell
72
, 681
–693
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
This content is only available via PDF.
© 1994 by Company of Biologists
1994
-JournalMeeting.png?versionId=3939)
(update)-InPreprints.png?versionId=3939)
-TechniquesAndResources.png?versionId=3939)
(update)-RashmiPriya.png?versionId=3939)
-NodeNetwork.png?versionId=3939)
