Laboratoire de Génétique du Développement et Evolution, Institut Jacques Monod, 2 Place Jussieu Tour 43, 75251 Paris Cedex 05, France
Author for correspondence (e-mail:
terracol{at}ijm.jussieu.fr)
Accepted 9 May 2003
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SUMMARY |
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Key words: vrille, Growth, Proliferation, Differentiation, Apoptosis, Cytoskeleton, Drosophila melanogaster
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INTRODUCTION |
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vri encodes a bZIP transcription factor
(George and Terracol, 1997)
with a typical basic DNA-binding domain and a leucine zipper involved in homo-
or heterodimerization (Vinson et al.,
1989
). Vri is closely related, in the bZIP extended domain, to
proteins implicated in cell death or growth. The more closely related factors
are, with 60% identity and 93% similarity with Vri, gene 9 of Xenopus
(Brown et al., 1996
) (which is
induced by thyroid hormone during the tadpole tail resorption program) and
E4BP4 (a transcription factor of the human placenta that acts as a repressor
of the protein E4 of adenovirus, which is involved in apoptosis)
(Cowell et al., 1992
;
Cowell and Hurst, 1994
). This
factor was later isolated as NFIL3A a transactivator of the interleukin 3
(IL3) promotor in human T cells (Zhang et
al., 1995
). In pro-B lymphocytes, the murine homolog of NFIL3A
(100% identity in the bZIP domain) is a delayed anti-apoptotic early
transcription factor induced by IL3 stimulation acting through the Ras/MAPK
(mitogen-activated protein kinase) and PI3K (phosphatidylinositol 3-kinase)
pathways. The alteration of these pathways is likely to contribute to human
B-lineage leukemia (Ikushima et al.,
1997
; Kuribara et al.,
1999
). Vri and NFIL3A are also related to the segmentation gap
gene product of Drosophila Giant
(Capovilla et al., 1992
), to
CES-2, the product of a cell death specification gene of C. elegans
(Metzstein et al., 1996
), and
to the sub-family of proteins (PAR) (Haas
et al., 1995
). In mammals, the PAR bZIP proteins include DBP
(Mueller et al., 1990
), TEF
(Drolet et al., 1991
), VBP
(Iyer et al., 1991
) and HLF
(hepatic leukemia factor) (Hunger et al.,
1992
). It has been postulated that members of the CES-2/PAR family
are evolutionarily conserved regulators of programmed cell death
(Metzstein et al., 1996
;
Seidel and Look, 2001
). In
other respects, it is noteworthy that the PAR family genes present, like
vri and the chicken and mouse homologs of NFIL3A/E4BP4, circadian
oscillations (Wuarin and Schibler,
1990
; Falvey et al.,
1995
; Fonjallaz et al.,
1996
; Blau and Young,
1999
; Mitsui et al.,
2001
; Doi et al.,
2001
).
We show that vri partial loss of function induces flight and other
locomotory defects associated with a downward bending wing phenotype and hair
defects. Furthermore, vri interacts genetically with genes encoding
actin-binding proteins: bent encoding a myosin light chain kinase
(Ayme-Southgate et al., 1991;
Daley et al., 1998
),
karst encoding a ßHeavy-spectrin
(Thomas and Kiehart, 1994
;
Thomas et al., 1998
;
Zarnescu and Thomas, 1999
),
and
actinin encoding an actin crosslinking spectrin
superfamily member (Fyrberg et al.,
1990
; Fyrberg et al.,
1998
; Roulier et al.,
1992
; Dubreuil and Wang,
2000
). Clonal analysis shows that vri is cell autonomous
and that the absence of vri reduces cell and hair size in wing and to
smaller eyes with a reduced number of ommatidia of abnormal morphology with
shorter photoreceptor cell stalks. The overexpression of vri reduces
salivary glands growth and nuclei size, a phenotype typical of an inhibition
of endoreplication. Overexpression of vri in the embryo and in
imaginal discs has an anti-proliferative effect. In the wing disc, increased
apoptosis is observed and at the wing surface cells with multiple trichomes
are formed, indicative of cell cycle arrest and defects in regulation of actin
cytoskeleton. We propose that vri may control cell growth and
proliferation via the regulation of the actin cytoskeleton.
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MATERIALS AND METHODS |
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DNA preparation, vri deficiency mapping
Standard molecular biology experiments were performed as described by
Sambrook et al. (Sambrook et al.,
1989). Genomic DNA preparations and PCR amplifications were
performed as described by Szuplewski and Terracol
(Szuplewski and Terracol,
2001
). Positions are from cDNA1 (3.8) start in the genomic region:
primer 1 (forward) 5'-CGATTGTCTGCACGCTGG-3' (322-339), primer 2
(reverse) 5'-GTTCCTTCTCCGGCGATC-3' (2570-2553), primer 3 (reverse)
5'-CAAGGCAAGGCTGGAGAG-3' (6083-6066) and primer 4 (reverse)
5'-AGTATCTGCAGCGCACGG-3' (7379-7352). P-lacW
(Bier et al., 1989
) primers:
5'P (reverse) 5'-CCTCTCAACAGCAAACGTGTACTG-3'
(90-67), 3'P (forward) 5'-TCTCTTGCCGACGGGACC-3'
(10653-10670), lacZ (forward) 5'-GATCATCTGGTCGCTGGG-3'
(1935-1952). vri5
(Török et al.,
1993
) was mapped by plasmid rescue
(George and Terracol, 1997
)
and upstream sequence from the 5'P primer is: (1218)
5'-GATTCTTGCATCATTCGGCG-3'. The insertion site is identical to
that determined from the P-lacW 3' end (AG034151) by the BDGP
(http://www.fruitfly.org/p_disrupt/)
(Spradling et al., 1995
;
Spradling et al., 1999
). PCR
products were cloned into pGEM plasmid (Promega) and sequenced with the SP6 or
T7 primers. PCR fragments and breakpoint sequences were:
vri5R7.2, 2.2 kb from primers lacZ-3;
P-lacW/genomic,
5'-GCAGTGCACGGCAGATACAC/TTGCCGCTTCGGTCACCCGT-3';
vri5R1.5, 3.3 kb from primers lacZ-4;
P-lacW/genomic,
5'-CAACATCAAATTGTCTGCGG/CGATGATGGTGAAGTTAACG-3';
vri5R5.24, cloned by plasmid rescue; and
genomic/P-lacW,
5'-TGATTTAAGCAGAGTATTTC/GCTAAATACTGGCAGGCGTT-3'. DNA was sequenced
by the dideoxy-chain termination method
(Sanger et al., 1977
) using
the US Biochemicals sequencing kit (Pharmacia) or performed on a ABI
PrismTM 377 DNA sequencer (Applied Systems). DNA sequences were
compiled using the Genetics Computer Group software (GCG)
(Devereux et al., 1984
) and
compared with the Drosophila database using the BDGP
(http://www.fruitfly.org/blast/)
Blast Searches program (Altschul et al.,
1990
).
Clonal analysis
Mitotic clones were generated using the FLP/FRT technique
(Golic and Lindquist, 1989;
Xu and Rubin, 1993
).
vri alleles were recombined onto a P[ry+ hs-neo
FRT]40A second chromosome. To generate somatic clones in adult y w/y
w; vri P[ry+ hs-neo-FRT]40A/CyO females were crossed to y
P[ry+ hs FLP]1/Y; P[y+] P[ry+ hs-neo FRT]40A/Bc
males and yellow clones analyzed in y P[ry+ hs FLP]1/y
w; P[y+] P[ry+ hs-neo FRT]40A/vri
P[ry+ hs-neo FRT]40A female progeny. Clones were heat-shock
induced at the third larval instar by 1 hour exposure at 38°C. To generate
mitotic clones in the eye, we used the EGUF/hid method
(Stowers and Schwarz, 1999
).
y w/y w; P[ry+ hs-neo FRT]40A GMR-hid l(2)CL-L1/CyO; ey-GAL4
UAS-FLP/ey-GAL4 UAS-FLP females were crossed to y w/Y;
vri P[ry+ hs-neo FRT]40A/CyO males at 29°C.
GAL4-expressing clones were induced by the FRT `flip-out' method
(Struhl and Basler, 1993
) by
crossing P[ry+ hs FLP]/Y; UAS-vri/SM6-TM6B (Tb) males to
Act5C>CD2>GAL4, UAS-GFP/Act5C>CD2>GAL4, UAS-GFP females.
In both types of experiments, clones were heat-shock induced in the progeny
10-48 hours after egg deposition by 30 minute exposure at 37°C.
Tb+ female larvae were dissected at mid third
larval instar.
Scanning electron microscopy, retina sections, embryonic and wing
phenotypic analyses
Flies were fixed in 3% glutaraldehyde, 0.1 M PBS (2 hours at room
temperature and then 24 hours at 4°C), dehydrated in ethanol series and
then in amyl acetate series. Electron microscopy was performed on a JEOL JSM
6100 scanning electron microscope. To observe adult retinas, flies were fixed
in carnoy, embedded in paraffin wax and 7 µm sections were cut on a Leica
RM 2145 microtome. Embryonic cuticles were prepared as described by Wieschaus
and Nüsslein-Volhard (Wieschaus and
Nüsslein-Volhard, 1986). Wings were dissected, collected in
70% ethanol and mounted in Euparal (Labosi).
Histology
Larval tissues were dissected in 1xPBS, fixed in PBT [1xPBS,
0.1% Tween 20 (Sigma) plus 4% paraformaldehyde] for 25 minutes, washed three
times for 5 minutes in PBT, stained for 10 minutes in PBT, 0.1 µg/ml DAPI
(Sigma), washed overnight in PBT, incubated 24 hours in 80% glycerol and
mounted in Citifluor (Kent Scientific Industry Project). Acridine Orange
(Sigma) staining was performed as described in Gaumer et al.
(Gaumer et al., 2000).
Preparations were observed on a Leica DMR fluorescence microscope using a
Micro Max (Princeton Instrument) camera and collected using the Metaview
Imaging System software (Universal Imaging Corporation).
UAS constructs and transformation experiments
vri cDNAs are described by George and Terracol
(George and Terracol, 1997).
The 3.8 kb XbaI fragment from pBScDNA3.8 was cloned into the
XbaI site of the pUAST transformation plasmid
(Brand and Perrimon, 1993
) and
the 3.3 kb SalI-XbaI fragment from pBScDNA3.3 was cloned
into the XhoI and XbaI sites of pUAST. pUAST constructs were
co-injected with the pUCh
2-3 helper plasmid in the pole cell region of
w1118 preblastoderm embryos
(Spradling and Rubin, 1982
).
20 UAS-vri1 (3.8 kb) and 27 UAS-vri2 (3.3 kb) independent
transformed lines were recovered. The following lines were used in this study:
UAS-vri16[III],
UAS-vri19[III],
UAS-vri113 [III],
UAS-vri114[X] and
UAS-vri28[II].
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RESULTS |
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vri affects wing shape and size, hair morphology and flight
and interacts with genes encoding actin-binding proteins
vri11 and vri13
over vri lethal alleles and Df(2L)tkvSz2
(25D2-4; 25D6-E1) lead to flies with pleiotropic phenotypes (100% penetrance).
The wings are shorter and downward (or more rarely upward) bending, and
posterior scutellar macrochaete are shorter and upturned
(Fig. 2A,B). They are poorly
viable and present locomotory and flight defects.
vri11/vri13 flies present the
same phenotypes. Wings are notably smaller and regions of atrophic or missing
hairs are present at the margin and on the surface of the wing
(Fig. 2C,D). The downward
bending phenotype has been described for other mutants. This is the case for
mutants in the arc gene, which encodes an adherens
junction-associated PDZ domain protein
(Liu and Lengyel, 2000) and in
the karst gene encoding ß-heavy-spectrin involved in cell
integrity, polarity and adhesion (Thomas
and Kiehart, 1994
; Thomas et
al., 1998
; Zarnescu and
Thomas, 1999
). This phenotype is also observed for mutations in
bent encoding a myosin light chain kinase expressed in indirect
flight muscle and tubular muscle
(Ayme-Southgate et al., 1991
;
Daley et al., 1998
). Viable
mutants in bent are flightless, this is also the case for mutants in
muscle actin, and in actin-binding proteins such as flightless I
encoding a gelsolin family homolog (Davy
et al., 2001
) and
actinin encoding an actin
crosslinking protein of the spectrin superfamily
(Fyrberg et al., 1990
;
Fyrberg et al., 1998
;
Roulier et al., 1992
;
Dubreuil and Wang, 2000
). We
have tested for interactions in double heterozygotes between vri and
arc, karst, bent and
actn alleles. No significant
interaction was observed with arc, but only the hypomorphic
a1 allele was tested. With the three other genes, reduced
viability and wing hair phenotypes similar to those of vri are
observed (Fig. 2E,F). With
bent (b1) and Actn8 (null),
Actn14 and ActnG0077, flies also
present progressive locomotory defects affecting rear legs.
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Overexpression of vri using the driver pannier, the
expression of which is restricted to dorsal tissues throughout development
(Calleja et al., 1996;
Heitzler et al., 1996
), leads
to embryonic lethality due to defects in the dorsal epidermis and dorsal
closure (Fig. 5B). Use of the
vg-GAL4 driver (Simmonds et al.,
1995
), which directs GAL4 expression in the wing pouch, leads to
notching at the wing margin (Fig.
5E). Overexpressing vri with the leaky
hsp70-GAL4 (Brand and Perrimon,
1993
) driver results in atrophic or missing bristles on the adult
cuticle (Fig. 5H). Similar
phenotypes are observed by overexpressing with the same drivers the inhibitor
of proliferation Rbf (Datar et al.,
2000
) (Fig. 5C,F,I)
or Rho1, a small GTPase involved in actin cytoskeleton regulation
(Hariharan et al., 1995
).
Overexpression of vri driven with ey-GAL4
(Hazelett et al., 1998
), the
expression of which is specific to the eye disc and starts in the embryonic
eye disc primordia, results in atrophy of the eye
(Fig. 6). We observed similar
phenotypes (not shown) by overexpressing Rbf
(Datar et al., 2000
) or Rho1
(Hariharan et al., 1995
).
According to the strength of the UAS-vri transgene and the
temperature, a progressive reduction in the size of the eye and a rough aspect
are observed (Fig. 6A-D). The
ommatidia are disorganized and bristles are either duplicated or missing. In
some flies, the eyes are totally absent
(Fig. 6E) and dissection of
third instar larvae revealed no eye disc and atrophic brain (not shown). The
stronger phenotype observed at 29°C leads to an absence of head
(Fig. 6F). These phenotypes are
compatible with an inhibition of proliferation.
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vri overexpression induces apoptosis and reduces cell size
and endoreplication
To observe the effect of vri overexpression at earlier stages,
larval tissues were studied. With the strong UAS-vri transgenes such
as UAS-vri19, their combination with MS1096-GAL4
is pupal lethal and leads to increased apoptosis in the undifferentiated
proliferating imaginal wing disc (Fig.
8A,B). Overexpression of vri was driven in the salivary
gland using the F4-GAL4 transgene whose expression starts in late
stage 13 of embryogenesis, once cell proliferation in the salivary primordium
is complete, between the first and second rounds of endoreplication. The
driver stays active throughout larval stages. F4-GAL4/+;
UAS-vri19/+ glands grow to about one half the size of the
control gland (Fig. 8C,D).
Nuclei are smaller indicating an inhibition of endoreplication and often
present a degenerative aspect characterized by a condensation of the chromatin
(pyknosis), suggestive of high levels of apoptosis. Overexpression in the fat
body, another polytenic tissue, using the `flip out' technique, results in
small clones with smaller cells, indicating an inhibition of endoreplication
(Fig. 8E,F).
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DISCUSSION |
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Smaller cells and bristles can result from metabolic defects, for example,
mutations in tRNAs, ribosomal proteins (Minute) or rRNAs. This is the
case for mutations in the S6 kinase gene, a regulator of ribosomal
protein production (Montagne et al.,
1999) and in Drosophila myc, diminutive, which is
involved in growth and metabolism
(Johnston et al., 1999
). They
are also found with genes regulating the cell cycle, such as rbf
(Datar et al., 2000
), and with
genes of the Ras/MAPK and Insulin/PI3K pathways controlling growth
(Stocker and Hafen, 2000
;
Oldham et al., 2000
;
Prober and Edgar, 2001
).
Hypomorphic mutations in the rbf gene, which encodes a homologue of
the retinoblastoma protein, Rb, an important regulator of cell proliferation
and differentiation leads to atrophic bristles and rough eyes
(Du, 2000
). Null-clone cells
in wing discs are smaller than wild-type cells and exhibit many pyknotic
nuclei, suggesting elevated levels of apoptosis. rbf-null clones
induced in the eye exhibit slight to moderate hypoplasia, missing or
duplicated bristles and fused ommatidia. However, RBF inhibits cell cycle
progression, rather than cellular growth directly
(Datar et al., 2000
). Cells
homozygous for partial loss-of-function mutations in components of the
Ras/MAPK pathway such as Ras1 grow slowly and remain small.
Ras1 controls growth, survival and differentiation in the eye
(Wassarman and Therrien,
1997
; Halfar et al.,
2001
) and coordinates cellular growth and cell cycle progression
in the wing (Diaz-Benjumea and Hafen,
1994
; Karim and Rubin,
1998
; Prober and Edgar,
2000
). Cells devoid of the lipid kinase PI3K
(Leevers et al., 1996
;
Weinkove et al., 1999
) have a
reduced growth and size, while loss of its antagonist dPTEN results in bigger
cells than wild type (Goberdhan et al.,
1999
; Huang et al.,
1999
; Gao et al.,
2000
).
Smaller cells and bristles can also result from cytoskeletal defects. For
example, the miniature and dusky genes encoding ZP proteins
required for cytoskeletal reorganization are involved in growth and
morphogenesis of cells and hairs in the wing
(Roch et al., 2003). Mutant
wings are smaller, phenotype also observed in vri viable
combinations. Drosophila bristles are single cells with very long
extensions supported by actin bundles of crosslinked actin filaments
(Tilney et al., 2000a
;
Tilney et al., 2000b
). The
assembly of actin filaments is under the control of the Rho GTPases, including
Rho1, Drac1 and DCdc42. Rho GTPases act as molecular switches
involved in many processes such as morphogenesis, chemotaxis, axonal guidance
and cell cycle progression (Hall,
1998
; Van Aelst and Symons,
2002
). They regulate actin cytoskeleton and are involved in planar
polarization, hair morphology and outgrowth processes
(Eaton et al., 1995
;
Eaton et al., 1996
;
Guichard et al., 1997
;
Hall, 1998
;
Adler et al., 2000
), and
photoreceptor morphogenesis. The dominant-negative form of Drac1, N17Drac1,
leads to reduced and disordered rhabdomeres
(Chang and Ready, 2000
;
Colley, 2000
), while
overexpression of Rho1 induces rough eyes and causes atrophy of the
retina (Hariharan et al.,
1995
). Regulation of actin cytoskeleton is coupled with other
pathways, including MAPK and PI3K pathways
(Hall, 1998
). For example
Drac1 acts upstream of JNK cascade and DCdc42 downstream of Dpp pathway in
dorsal and thorax closure processes (Ricos
et al., 1999
). lilli acts in cytoskeleton regulation,
control of cell identity and cell growth, in parallel with the Ras/MAPK and
PI3K/PKB pathways. It is noteworthy that retinal cells and wing margin
bristles lacking lilly are significantly smaller than wild type
(Wittwer et al., 2001
;
Tang et al., 2001
). The
flightless I-mediated cytoskeletal regulation involves PI3K, and the small
GTPases Ras, RhoA and Cdc42 (Davy et al.,
2001
). Viable mutations in flightless I cause also
ultrastructural defects in the indirect flight muscles.
vri overexpression inhibits proliferation and alters
cytoskeleton regulation and endoreplication
Overexpression of vri in the embryo and imaginal discs induces an
atrophy of the resulting tissues. With strong transgenes, the discs do not
proliferate and the adult structures are totally absent. Similar phenotypes
are observed when the inhibitor of proliferation Rbf or the regulator of actin
cytoskeleton Rho1 are overexpressed. In wing discs, strong transgenes lead to
lethality and increased apoptosis is observed. On the wing surface larger
cells with multiple trichomes are observed. With strong viable transgenes, the
wing is reduced and trichomes are disoriented with abnormal morphology. This
phenotype has been attributed to cell cycle arrest in G1 phase. Inactivation
of Cdc2 kinase which regulates entry into mitosis or of the myb gene
required for G2/M transition and maintenance of diploidy leads to a similar
phenotype (Weigmann et al.,
1997; Katzen et al.,
1998
). This phenotype is observed when the human cyclin-dependant
kinase inhibitor P21CIP/WAF1 is overexpressed with UASP21 driven by
the dpp-GAL4 transgene (Karim and
Rubin, 1998
). We observed the same phenotype when overexpressing
dacapo, the Drosophila P21 homolog
(De Nooij et al., 1996
), under
the control of MS1096-GAL4. DAP binds to Cyclin E/Cdk2 complexes
inducing cell cycle arrest in G1 phase and epidermal cell proliferation
inhibition (Lane et al.,
1996
). The same phenotype is also observed when disrupting
cytoskeleton regulation by overexpressing the activated form of Drac1,
DRac1N17 (Eaton et al., 1995
)
or a dominant-negative form of DRacGAP,
DRacGAP
EIE. DRacGAP is a negative regulator of
the Rho-family GTPases, Drac1 and DCdc42, regulating actin cytoskeleton via
EGF/Ras signaling pathway in the developing wing. The P21 overexpression
phenotype is suppressed by UAS-Ras1V12, an activated form
of Ras1, or UAS-DRacGAP (Sotillos
and Campuzano, 2000
).
In salivary glands, vri overexpression leads to glands whose size
is reduced by about one half with numerous pyknotic nuclei, suggesting
inhibition of endoreplication and elevated levels of apoptosis. A reduction in
the size of the gland and an inhibition of the level of endoreplication is
observed when the genes encoding cell cycle regulators cyclin E,
dacapo (Follette et al.,
1998; Weiss et al.,
1998
) and rbf (Datar
et al., 2000
) are overexpressed. Pulses of Cyclin E are required
to drive endocycle S phase, and continuous expression inhibits endoreplication
cycles. In the fat body (polytenic tissue), vri-overexpressing clones
are small with smaller cells often presenting a degenerative aspect.
Possible level of vri function
vri was previously identified as an enhancer of dpp
phenotypes both in embryo and adult
(George and Terracol, 1997).
dpp encodes a TGFß homolog closely related to BMP4 (bone
morphogenetic protein 4), which acts as a morphogen at different stages of
development (reviewed by Podos and
Ferguson, 1999
). Dpp plays a proliferative role in all imaginal
discs at larval stages but induces a cell cycle arrest in G1 phase in the
eye-antennal disc during third larval instar
(Horsfield et al., 1998
). Dpp
might promote cell growth and/or proliferation directly, in a cell-autonomous
manner (Burke and Basler, 1996
;
Martin-Castellanos and Edgar,
2002
). Other genes have been identified or described as enhancers
of dpp phenotypes. Some of them are integral members of the
dpp pathway, which is the case for tkv
(Terracol and Lengyel, 1994
),
Mad and Med (Raftery et
al., 1995
), but others [such as lilliputian
(Su et al., 2001
) and
cyclope (Szuplewski and
Terracol, 2001
)] have been shown to act in different pathways.
Interestingly, lilli has been also identified in other screens as a
dominant suppressor of activated MAP kinase pathway phenotypes
(Dickson et al., 1996
;
Neufeld et al., 1998b
;
Rebay et al., 2000
).
lilli acts in parallel with the Ras/MAPK and PI3K/PKB pathways in the
control of cell identity, cell growth and/or cytoskeletal arrangement
(Wittwer et al., 2001
;
Tang et al., 2001
).
vri mutations do not alter dpp pathway target gene
expression and probably act in a parallel pathway.
vri overexpression phenotypes suggest a role in cell cycle and proliferation. However, these phenotypes are not rescued by simultaneous overexpression of the genes encoding activators of proliferation, Drosophila E2F, cyclin E or string. Therefore, it is unlikely that Vri is either a direct repressor of genes that activate proliferation or an activator of those acting as inhibitors of proliferation like rbf or dacapo. It could act upstream in the Ras/MAPK or PI3K pathways regulating growth and involved in the regulation of the mammalian homolog of Vri, NFIL3A, acting mostly as a repressor. Genetic interactions have been tested in double-heterozygotes with available members of these pathways and vri, but no reduction in viability nor any strong phenotypes was recovered. This could result from genes with non-limiting products and/or be due to the functional redundancy of vri. Alternatively, vri may control cell size independently of growth signals.
vri loss-of-function and overexpression phenotypes, more probably,
could result from primary defects in cytoskeletal actin network. Although
cytoskeletal integrity and adhesion are altered in mutants of regulators of
cell growth and proliferation, these effects are indirect. Wing hair atrophy
phenotypes were observed in interaction with the karst gene involved
in cytoskeleton arrangement. The downward-bending wing and the reduction of
the photoreceptor stalk size (Pellikka et
al., 2002) are two other phenotypes observed in vri and
kst. We observed new vri phenotypes affecting wing shape
flight and locomotion. Locomotory defects could result from neurological or
muscular alteration (or both). We found interaction with the
actn and bent genes involved in muscle actin function, which
suggests that the effect is rather at the muscular level, although we have not
observed gross defect in indirect flight muscle. However these defects appear
degenerative and must be studied in more detail. We also observe hair atrophic
phenotypes in interaction with these two genes, suggesting an effect in other
cell types. Although the locomotory and hair defects are not necessarily
related, it is notable that the genes interacting with vri affect
different types of actin, muscle and non-muscle actin. It will be interesting
to search for the direct targets of Vri to understand its implication in
locomotion and cytoskeletal integrity.
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ACKNOWLEDGMENTS |
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Footnotes |
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A.,
Gocayne, J. D., Amanatides, P. G., Scherer, S. E., Li, P. W., Hoskins, R. A.,
Galle, R. F. et al. (2000). The sequence of Drosophila
melanogaster. Science
287,2185
-2195.
Adler, P. N., Liu, J. and Charlton, J. (2000). Cell size and the morphogenesis of wing hairs in Drosophila. Genesis 28,82 -91.[CrossRef][Medline]
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. and Lipman, D. J. (1990). Basic local aligment search tool. J. Mol. Biol. 215,403 -410.[CrossRef][Medline]
Ayme-Southgate, A., Vigoreaux, J., Benian, G. and Pardue, M. L. (1991). Drosophila has a twitchin/titin-related gene that appears to encode projectin. Proc. Natl. Acad. Sci. USA 88,7973 -7977.[Abstract]
Bier, E., Vaessin, H., Shepherd, S., Lee, K., McCall, K., Barbel, S., Ackerman, L., Carretto, R., Uemura, T., Grell, E., Jan, L. Y. and Jan, Y. N. (1989). Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. Genes Dev. 3,1273 -1287.[Abstract]
Blau, J. and Young, M. W. (1999). Cycling vrille expression is required for functional Drosophila clock. Cell 99,661 -671.[Medline]
Brand, A. H. and Perrimon, N. (1993). Targeted
gene expression as a means of altering cell fates and generating dominant
phenotypes. Development
118,401
-405.
Brown, D. D., Wang, Z., Furlow, J. D., Kanamori, A.,
Schwartzman, R. A., Remo, B. F. and Pinder, A. (1996). The
thyroid hormone-induced tail resorption program during Xenopus laevis
metamorphosis. Proc. Natl. Acad. Sci. USA
93,1924
-1929.
Burke, R. and Basler, K. (1996). Dpp receptors
are autonomously required for cell proliferation in the entire developing
Drosophila wing. Development
122,2261
-2269.
Calleja, M., Moreno, E., Pelaz, S. and Morata, G.
(1996). Vizualization of gene expression in living adult
Drosophila. Science
274,252
-255.
Capdevila, J. and Guerrero, I. (1994). Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 13,4459 -4468.[Abstract]
Capovilla, M., Eldon, E. D. and Pirrotta, V. (1992). The giant gene of Drosophila encodes a b-ZIP DNA-binding protein that regulates expression of other segmentation gap genes. Development 114,99 -112.[Abstract]
Chang, H-Y. and Ready, D. F. (2000). Rescue of
photoreceptor degeneration in rhodopsin-null Drosophila mutants by
activated Rac1. Science
290,1978
-1980.
Colley, N. J. (2000). Actin'up with Rac1.
Science 290,1902
-1903.
Cowell, I. G. and Hurst, H. C. (1994). Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res. 22, 59-65.[Abstract]
Cowell, I. G., Skinner, A. and Hurst, H. C. (1992). Transcriptional repression by a novel member of the bZIP family of transcription factors. Mol. Cell. Biol. 12,3070 -3077.[Abstract]
Cyran, S. A., Buchsbaum, A. M., Reddy, K. L., Lin, M-C., Glossop, N. R. J., Hardin, P. E., Joung, M. W., Storti, R. V. and Blau, J. (2003). vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell 112,329 -341.[Medline]
Daley, J., Southgate, R. and Ayme-Southgate, A. (1998). Structure of the Drosophila projectin protein: isoforms and implication for projectin filament assembly. J. Mol. Biol. 279,201 -210.[CrossRef][Medline]
Datar, S. A., Jacobs, H. W., de la Cruz, A. F., Lehner, C. F.
and Edgar B. (2000). The Drosophila Cyclin D-Cdk4
complex promotes cellular growth. EMBO J.
19,4543
-4554.
Davy, D. A., Campbell, H. D., Fountain, S., de Jung, D. and
Crouch, M. F. (2001). The flightless I protein colocalizes
with actin-and microtubule-based structures in motile Swiss 3T3 fibroblasts:
evidence for the involvement of PI3-kinase and Ras-related small GTPases.
J. Cell. Sci. 114,549
-562.
De Nooij, J. C., Letendre, M. A. and Hariharan, I. K. (1996). A cyclindependant kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell 87,1237 -1247.[Medline]
Devereux, J., Haeberli, P. and Smithies, O. (1984). A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 12,387 -395.[Abstract]
Diaz-Benjumea, F. J. and Hafen, E. (1994). The
sevenless signalling cassette mediates Drosophila EGF receptor
function during epidermal development. Development
120,569
-578.
Dickson, B., van der Straten, A., Dominguez, M. and Hafen,
E. (1996). Mutations modulating Raf signaling in
Drosophila eye development. Genetics
142,163
-171.
Doi, M., Nakajima, Y., Okano, T. and Fukada, Y.
(2001). Light-induced phase-delay of the chicken pineal circadian
clock is associated with the induction of cE4bp4, a potential
transcriptional repressor of cPer2 gene. Proc. Natl. Acad.
Sci. USA 98,8089
-8094.
Drolet, D. W., Scully, K. M., Simmons, D. M., Wegner, M., Chu, K., Swanson, L. W. and Rosenfeld, M. G. (1991). TEF, a transcription factor expressed specifically in the anterior pituitary during embryogenesis, defines a new class of leucine zipper proteins. Genes Dev. 5,1739 -1753.[Abstract]
Du, W. (2000). Suppression of the rbf
null mutants by a de2f1 allele that lacks transactivation domain.
Development 127,367
-379.
Du, W. and Dyson, N. (1999). The role of RBF in
the introduction of G1 regulation during Drosophila embryogenesis.
EMBO J. 18,916
-925.
Du, W., Vidal, M., Xie, J. and Dyson, N. (1996). RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila. Genes Dev. 10,1206 -1218.[Abstract]
Dubreuil, R. R. and Wang, P. (2000). Genetic
analysis of the requirements for -actinin function. J.
Muscle Res. Cell Motility 21,705
-713.[Medline]
Duronio, R. J. and O'Farrell, P. (1995). Developmental control of the G1 to S transition in Drosophila: cyclin E is a limiting downstream target of E2F. Genes Dev. 9,1456 -1468.[Abstract]
Duronio, R. J., O'Farrell, P., Xie, J-E., Brook, A. and Dyson, N. (1995). The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev. 9,1445 -1455.[Abstract]
Eaton, S., Auvinen, P., Luo, L., Jan, Y. N. and Simons, K. (1995). CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium. J. Cell Biol. 131,151 -164.[Abstract]
Eaton, S., Wepf, R. and Simons, K. (1996). Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila. J. Cell Biol. 135,1277 -1289.[Abstract]
Falvey, E., Fleury-Olela, F. and Schibler, U. (1995). The rat hepatic leukemia factor (HLF) gene encodes two transcriptional activators with distinct circadian rhythms, tissue distributions and target preferences. EMBO J. 14,4307 -4317.[Abstract]
FlyBase (2003). The FlyBase database of the
Drosophila genome projects and community literature. Nucleic Acids
Res. 31,172
-175.
Follette, P. J., Duronio, R. J. and O'Farrell, P. H. (1998). Fluctuations in Cyclin E levels are required for multiple rounds of endocycle S phase Drosophila. Curr. Biol. 8,235 -238.[Medline]
Fonjallaz, P., Ossipow, V., Wanner, G. and Schibler, U. (1996). The two PAR leucine zipper proteins, TEF and DBP, display similar circadian and tissue-specific expression, but have different target promoter preferences. EMBO J. 15,351 -362.[Abstract]
Fyrberg, E., Kelly, M., Ball, E., Fyrberg, C. and Reedy, M. C. (1990). Molecular genetics of Drosophila Alpha-actinin: mutant alleles disrupt Z disc integrity and muscle insertions. J. Cell Biol. 110,1999 -2011.[Abstract]
Fyrberg, C., Ketchum, A., Ball, E. and Fyrberg, E.
(1998). Characterization of lethal Drosophila
melanogaster Actinin mutants. Biochem.
Genet. 36,299
-310.[CrossRef][Medline]
Gao, X., Neufeld, T. N. and Pan, D. (2000). Drosophila PTEN regulates cell growth and proliferation through PI3K-dependant and -independant pathways Dev. Biol. 221,404 -418.[CrossRef][Medline]
Gaumer, S., Guénal, I., Brun, S., Théodore, L. and Mignotte, B. (2000). Bcl2 and Bax mammalian regulators of apoptosis are functional in Drosophila. Cell Death Differ. 7,804 -814.[CrossRef][Medline]
George, H. and Terracol, R. (1997). The
vrille gene of Drosophila is a maternal enhancer of
decapentaplegic and encodes a new member of the bZIP family of
transcription factors. Genetics
146,1345
-1363.
Glossop, N. R. J., Houl, J. H., Zheng, H., Ng, F. S., Dubek, S. M. and Hardin, P. E. (2003). VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator. Neuron 37,249 -261.[Medline]
Goberdhan, D. C. I., Patricio, N., Goodman, E. C., Mlodzick, M.
and Wilson, C. (1999). Drosophila tumor suppressor
PTEN control cell size and number by antagonizing the
Chico/PI3-kinase signaling pathway. Genes Dev.
13,3244
-3258.
Golic, K. G. and Lindquist, S. (1989). The FLP recombinase of yeast catalizes site-specific recombination in the Drosophila genome. Cell 59,499 -509.[Medline]
Guichard, A., Bergeret, E. and Griffin-Shea, R. (1997). Overexpression of RnRacGap in Drosophila melanogaster deregulates cytoskeletal organisation in cellularising embryos and induces discrete imaginal phenotypes. Mech. Dev. 61,49 -62.[CrossRef][Medline]
Guillén, I., Mullor, J. L., Capdevilla, J.,
Sànchez-Herrero, E., Morata, G. and Guerrero, I.
(1995). The function of engrailed and the specification
of Drosophila wing pattern. Development
121,3447
-3456.
Haas, N. B., Cantwell, C. A., Johnson, P. F. and Burch, J. B. E. (1995). DNA-binding specificity of the PAR basic leucine zipper protein VBP partially overlaps those of the C/EBP and CREB/ATF families and is influenced by domains that flank the core basic region. Mol. Cell. Biol. 15,1923 -1932.[Abstract]
Haerry, T. E., Khalsa, O., O'Connor, M. B. and Wharton, K.
A. (1998). Synergistic signaling by two BMP ligands through
the SAX and TKV receptors controls wing growth and patterning in
Drosophila. Development
125,3977
-3987.
Halfar, K., Rommel, C., Stocker, H. and Hafen, E. (2001). Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development 126,1667 -1696.
Hall, A. (1998). Rho GTPases and the actin
cytoskeleton. Science
279,509
-514.
Hariharan, I. K., Hu, K-Q., Asha, H., Quintanilla, A., Ezzell, R. M. and Settleman, J. (1995). Characterization of rho GTPase family homologues in Drosophila melanogaster: overexpressing Rho1 in retinal cells causes a late developmental defect. EMBO J. 14,292 -302.[Abstract]
Hazelett, D. J., Bourouis, M., Walldorf, U. and Treisman, J.
(1998). decapentaplegic and wingless are
regulated by eye absent and eyegone and interact to direct
the pattern of retinal differentiation in the eye disc.
Development 125,3741
-3751.
Heitzler, P., Haenlin, M., Ramain, P., Calleja, M. and Simpson,
P. (1996). A genetic analysis of pannier, a gene
necessary for viability of dorsal tissues and bristle positioning in
Drosophila. Genetics
143,1271
-1286.
Horsfield, J., Penton, A., Secombe, J., Hoffman, M. and
Richardson, H. (1998). decapentaplegic is required
for arrest in G1 phase during Drosophila eye development.
Development 125,5069
-5078.
Huang, H., Potter, C. J., Tao, W., Li, D., Brogiolo, W., Hafen,
H., Sun, H. and Xu, T. (1999). PTEN affects cell size, cell
proliferation and apoptosis during Drosophila eye development.
Development 126,5365
-5372.
Hunger, S. P., Ohyashiki, K., Toyama, K. and Clearly, M. L. (1992). Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19). acute lymphoblastic leukemia. Genes Dev. 6,1608 -1620.[Abstract]
Ikushima, S., Inukai, T., Inaba, T., Nimer, S. D., Cleveland, J.
L. and Look, A. T. (1997). Pivotal role for the NFIL3/E4BP4
transcription factor in interleukin 3-mediated survival of pro-B lymphocytes.
Proc. Natl. Acad. Sci. USA
94,2609
-2614.
Iyer, S. V., Davis, D. L., Seal, S. N. and Burch, J. B. E. (1991). Chicken vitellogenin gene-binding protein, a leucine zipper transcription factor that binds to an important control element in the chicken vitellogenin II promoter, is related to rat DBP. Mol. Cell. Biol. 11,4863 -4875.[Medline]
Jiao, R., Daube, M., Duan, H., Zou, Y., Frei, E. and Noll,
M. (2001). Headless flies generated by developmental pathway
interference. Development
128,3307
-3319.
Johnston, L. A., Prober, D. A., Eisenman, R. N. and Gallant, P. (1999). Drosophila myc regulates cellular growth during development. Cell 98,779 -790.[Medline]
Karim, F. D. and Rubin, G. M. (1998). Ectopic
expression of activated Ras1 induces hyperplastic growth and increased cell
death in Drosophila imaginal tissues.
Development 125,1
-9.
Katzen, A. L., Jackson, J., Harmon, B. P., Fung, S-M., Ramsay,
G. and Bishop, J. M. (1998). Drosophila myb is
required for the G2/M transition and the maintenance of diploidy.
Genes Dev. 12,831
-843.
Kuribara, R., Kinoshita, T., Miyajima, A., Shinjyo, T.,
Yoshihara, T., Inukai, T., Ozawa, K., Look, A. T. and Inaba, T.
(1999). Two distinct interleukin-3 signal pathways, Ras-NFIL3
(E4BP4) and Bcl-xL, regulate the survival of murine pro-B
lymphocytes. Mol. Cell. Biol.
19,2754
-2762.
Lane, M. E., Sauer, K., Wallace, K., Jan, Y. N., Lehner, C. F. and Vaessin, H. (1996). Dacapo, a Cyclin-dependant kinase inhibitor, stops cell proliferation during Drosophila development. Cell 87,1225 -1235.[Medline]
Leevers, S. J., Weinkove, D., MacDougall, L. K., Hafen, E. and Waterfield, M. D. (1996). The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J. 15,6584 -6594.[Abstract]
Lindsley, D. L. and Zimm, G. G. (1992).The Genome of Drosophila melanogaster . San Diego: Academic Press.
Liu, X. and Lengyel, J. A. (2000). Drosophila arc encodes a novel adherens junction-associated PDZ domain protein required for wing and eye development. Dev. Biol. 221,419 -434.[CrossRef][Medline]
Martin-Castellanos, C. and Edgar, B. A. (2002). A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development 129,1003 -1013.[Medline]
Metzstein, M. M., Hengartner, M. O., Tsung, N., Ellis, R. E. and Horvitz, H. R. (1996). Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Nature 382,545 -547.[CrossRef][Medline]
Mitsui, S., Yamaguchi, S., Matsuo, T., Ishida, Y. and Okamura,
H. (2001). Antagonistic role of E4BP4 and PAR proteins in the
circadian oscillatory mechanism. Genes Dev.
15,995
-1006.
Montagne, J., Stewart, M. J., Stocker, H., Hafen, E., Kozma, S.
C. and Thomas, G. (1999). Drosophila S6 kinase: A
regulator of cell size. Science
285,2126
-2129.
Mueller, C. R., Maire, P. and Schibler, U. (1990). DBP, a rat liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined postranscriptionally. Cell 61,279 -291.[Medline]
Neufeld, T. P., de la Cruz, A. F. A., Johnston, L. A. and Edgar, B. A. (1998a). Coordination of growth and cell division in the Drosophila wing. Cell 93,1183 -1193.[Medline]
Neufeld, T., Tang, A. and Rubin, G. (1998b). A
genetic screen to identify components of the sina signaling pathway
in Drosophila eye development. Genetics
148,277
-286.
Oldham, S., Böhni, R., Stocker, H., Brogiolo, W. and Hafen, H. (2000). Genetic control of size in Drosophila. Philos. Trans. R. Soc. Lond. B 355,945 -952.[CrossRef][Medline]
Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C. J., Ready, D. F. and Tepass, U. (2002). Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Nature 416,143 -149.[CrossRef][Medline]
Podos, S. D. and Fergusson, E. L. (1999). Morphogen gradients new insights from DPP. Trends Genet. 15,396 -402.[CrossRef][Medline]
Prober, D. A. and Edgar, B. A. (2000). Ras1 promotes cellular growth in the Drosophila wing. Cell 100,435 -446.[Medline]
Prober, D. A. and Edgar, B. A. (2001). Growth regulation by oncogenes new insights from model organisms. Curr. Opin. Genet. Dev. 11, 19-26.[CrossRef][Medline]
Raftery, L., Twombly, V., Warthon, K. and Gelbart, W.
(1995). Genetic screen to identify elements of the dpp
pathway in Drosophila. Genetics
139,241
-254.
Rebay, I., Chen, F., Hsiao, F., Kolodziej, P. A., Kuang, B. H.,
Laverty, T., Suh, C., Voas, M., Williams, A. and Rubin, G. M.
(2000). A genetic screen for novel components of the
Ras/mitogen-activated protein kinase signaling pathway that interact with the
yan gene of Drosophila identifies split ends, a new RNA recognition
motif-containing protein. Genetics
154,695
-712.
Ricos, M. G., Harden, N., Sem, K. P., Lim, L. and Chia, W.
(1999). Dcdc42 acts in TGF-ß signaling during Drosophila
morphogenesis: distinct roles for the Drac1/JNK and Dcdc42/TGF-ß cascades
in cytoskeletal regulation. J. Cell Sci.
112,1225
-1235.
Roch, F., Alonso, C. R. and Akam, M. (2003).
Drosophila miniature and dusty encodes ZP proteins required
for cytological reorganisation during wing morphogenesis. J. Cell
Sci. 116,1199
-1207.
Roulier, E. M., Fyrberg, C. and Fyrberg, E.
(1992). Perturbations of Drosophila -Actinin
cause muscle paralysis, weakness, and atrophy but do not confer obvious
nonmuscle phenotypes. J. Cell Biol.
116,911
-922.[Abstract]
Rubin, G. M., Hong, L., Brokstein, P., Evans-Holm, M., Frise,
E., Stapleton, M. and Harvey, D. A. (2000). A
Drosophila complementary DNA resource.
Science 287,2222
-2224.
Sambrook, J., Fritsch, E. F. and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
Sanger, F., Nicklen, S. and Coulson, A. R. (1977). DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74,5463 -5467.[Abstract]
Seidel, M. G. and Look, A. T. (2001). E2A-HLF usurps control of evolutionarily conserved survival pathways. Oncogene 20,5718 -5725.[CrossRef][Medline]
Simmonds, A. J., Brook, W. J., Cohen, S. M. and Bell, J. B. (1995). Distinguishable functions for engrailed and invected in anterior-posterior patterning in the Drosophila wing. Nature 376,424 -427.[CrossRef][Medline]
Sotillos, S. and Campuzano, S. (2000).
DRacGAP, a novel Drosophila gene, inhibits EGFR/Ras
signalling in the developing imaginal wing disc.
Development 127,5427
-5438.
Spradling, A. C. and Rubin, G. M. (1982). Transposition of cloned P elements into Drosophila germ line chromosomes. Science 218,348 -353.[Medline]
Spradling, A. C., Stern, D. M., Kiss, I., Roote, J., Laverty, T. and Rubin, G. M. (1995). Gene disruptions using P transposable elements: An integral component of the Drosophila genome project. Proc. Natl. Acad. Sci. USA 92,10824 -10830.[Abstract]
Spradling, A. C., Stern, D. A., Beaton, A., Rhem, E. J.,
Laverty, T., Mozden, N., Misra, S. and Rubin, G. M. (1999).
The Berkeley Drosophila Genome Project gene disruption project:
single P-element insertions mutating 25% of vital Drosophila
genes. Genetics 153,135
-177.
Stocker, H. and Hafen, E. (2000). Genetic control of cell size. Curr. Opin. Genet. Dev. 10,529 -535.[CrossRef][Medline]
Stowers, R. S. and Schwarz, T. L. (1999). A
genetic method for generating Drosophila eyes composed exclusively of
mitotic clones of a single genotype. Genetics
152,1631
-1639.
Struhl, G. and Basler, K. (1993). Organizing activity of wingless protein in Drosophila. Cell 72,527 -540.[Medline]
Su, M. A., Wisotzkey, R. G. and Newfeld, S. J.
(2001). A screen for modifiers of decapentaplegic mutant
phenotypes identifies lilliputian, the only member of the
fragile-X/Burkitt's lymphoma family of transcription factors in Drosophila
melanogaster. Genetics
157,717
-725.
Szuplewski, S. and Terracol, R. (2001). The
cyclope gene of Drosophila encodes a cytochrome c oxidase
subunit VIc homolog. Genetics
158,1629
-1643.
Tang, A. H., Neufeld, T. P., Rubin, G. M. and Müller, H. A.
J. (2001). Transcriptional regulation of cytoskeletal
functions and segmentation by a novel maternal pair-rule gene,
lilliputian. Development
128,801
-813.
Terracol, R. and Lengyel, J. A. (1994). The
thick veins gene of Drosophila is required for dorsoventral
polarity of the embryo. Genetics
138,165
-178.
Thomas, G. H. and Kiehart, D. P. (1994).
ßHeavy-spectrin has a restricted tissue and subcellular distribution
during Drosophila embryogenesis. Development
120,2039
-2050.
Thomas, G. H., Zarnescu, D. C., Juedes, A. E., Bales, M. A.,
Londergan, A., Korte, C. C. and Kiehart, D. P. (1998)
Drosophila ßHeavy-spectrin is essential for development and
contributes to specific cell fates in the eye.
Development 125,2125
-2134.
Tilney, L. G., Connelly, P. S., Vranich, K. A., Shaw, M. K. and
Guild, G. M. (2000a). Regulation of Actin filament
cross-linking and bundle shape in Drosophila bristles. J.
Cell Biol. 148,87
-99.
Tilney, L. G., Connelly, P. S., Vranich, K. A., Shaw, M. K. and
Guild, G. M. (2000b). Actin filaments and microtubules play
different roles during bristle elongation in Drosophila.
J. Cell Sci. 113,1255
-1265.
Török, T., Tick, G., Alvarado, M. and Kiss, I.
(1993). P-lacW insertional mutagenesis on the second
chromosome of Drosophila melanogaster: isolation of lethals with
different overgrowth phenotypes. Genetics
135, 71-80.
Van Aelst, L. and Symons, M. (2002). Role of
Rho family GTPases in epithelium morphogenesis. Genes.
Dev. 16,1032
-1054.
Vinson, C. R., Sigler, P. B. and McKnight, S. L. (1989). Scissors-grip model for DNA recognition by a family of leucine zipper proteins. Science 246,911 -916.[Medline]
Wassarman, D. A. and Therrien, M. (1997). RAS1-mediated phosphoreceptor development in Drosophila. Adv. Dev. Biol. 5,1 -41.
Weigmann, K., Cohen, S. M. and Lehner, C. F.
(1997). Cell cycle progression, growth and patterning in the
imaginal discs despite inhibition of cell division after inactivation of
Drosophila Cdc2 kinase. Development
124,3555
-3563.
Weinkove, D., Neufeld, T. P., Twardzik, T., Waterfield, M. D. and Leevers, S. J. (1999). Regulation of imaginal disc cell size, cell number and organ size by Drosophila class IA phosphoinositide 3-kinase and its adaptator. Curr. Biol. 9,1019 -1029.[CrossRef][Medline]
Weiss, A., Herzig, A., Jacobs, H. and Lehner, C. (1998). Continuous Cyclin E expression inhibits progression through endoreplication cycles in Drosophila. Curr. Biol. 8,239 -242.[Medline]
Wieschaus, E. and Nüsslein-Volhard, C. (1986). Looking at embryos. In Drosophila A Practical Approach (ed. D. M. Roberts), pp.199 -227. Oxford: IRL Press.
Wittwer, F., van der Straten, A., Keleman, K., Dickson, B. J.
and Hafen, E. (2001). Lilliputian: an AF4/FMR2-related
protein that controls cell identity and cell growth.
Development 128,791
-800.
Wuarin, J. and Schibler, U. (1990). Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. Cell 63,1257 -1266.[Medline]
Xu, T. and Rubin, G. M. (1993). Analysis of
genetic mosaics in developing and adult Drosophila tissues.
Development 117,1223
-1237.
Zarnescu, D. C. and Thomas, G. H. (1999).
Apical spectrin is essential for epithelial morphogenesis but not apicobasal
polarity in Drosophila. J. Cell Biol.
146,1075
-1086.
Zhang, W., Zhang, J., Kornuc, M., Kwan, K., Frank, R. and Nimer, S. D. (1995). Molecular cloning and characterization of NF-IL3A, a transcriptional activator of the human interleukin-3 promoter. Mol. Cell. Biol. 15,6055 -6063.[Abstract]