Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue 68-230B, Cambridge, MA 02139, USA
* Author for correspondence (e-mail: pgarrity{at}mit.edu)
Accepted 14 July 2004
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SUMMARY |
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Key words: Nuclear migration, Dynein, Capping protein, Dynamitin, Kinesin
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Introduction |
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Nuclear positioning makes an important contribution to brain architecture.
In insects, for example, neuronal nuclei and neuronal processes are spatially
segregated within the brain, with nuclei populating cortical regions while
neurites extend into neuropil regions and establish connections
(Cajal, 1990;
Strausfeld and Meinertzhagen,
1998
). While such extreme spatial segregation is not as widely
observed in mammals, neuronal nuclear positions are highly stereotyped
throughout the mammalian nervous system
(Cajal, 1990
;
Strausfeld and Meinertzhagen,
1998
). Genes mutated in several human neurological disorders
(including isolated lissencephaly sequence, MillerDieker syndrome, and
some forms of lissencephaly with cerebellar hypoplasia) have been implicated
in nuclear positioning in other systems
(Gupta et al., 2002
;
Olson and Walsh, 2002
),
although whether defects in the maintenance of nuclear positioning within
neurons contribute to these disorders is unknown. Nonetheless, functional
studies of these genes in model organisms suggest that the molecular
mechanisms that control nuclear positioning may be relevant to human neuronal
mispositioning disorders (Morris,
2003
; Reinsch and Gonczy,
1998
).
Their highly polarized nature and complex morphologies make neurons a
favorable system for studying nuclear positioning, yet the mechanisms that
maintain nuclear position in postmitotic neurons have not been extensively
explored. Both the microtubule cytoskeleton and the actin cytoskeleton have
been implicated in positioning nuclei within non-motile animal cells
(Starr and Han, 2003). The
nucleus is often associated with the focus of microtubule minus ends, and work
in non-dividing cultured mammalian cells indicates that the cytoplasmic
microtubule network and the minus-end directed microtubule motor Dynein are
important for maintaining the focus of microtubule minus ends and nuclear
position (Quintyne et al.,
1999
). In multinucleate Caenorhabditis elegans muscle
cells and in Drosophila melanogaster nurse cells, nuclei require
anchorage to the actin cytoskeleton to maintain their appropriate positions
(Starr and Han, 2003
).
In the D. melanogaster compound eye, the precise packing of
photoreceptor neurons within each facet of the eye involves the highly
stereotyped localization of photoreceptor nuclei. The photoreceptors are
generated within a polarized monolayer epithelium (the eye imaginal disc), and
the coordinated movements of differentiating photoreceptor nuclei have been
described in detail (Tomlinson,
1985). As each photoreceptor differentiates, its nucleus rises
toward the apical surface of the eye disc and remains apical while the
photoreceptor axon extends toward the basal surface of the eye disc and into
the brain. Several mutations that cause photoreceptor nuclei to be displaced
toward the brain have been identified and include mutations in genes encoding
the Dynactin subunit Glued (Fan and Ready,
1997
), the Dynein-associated protein Lis1
(Swan et al., 1999
) (the human
homolog of which is disrupted in isolated lissencephaly sequence and
MillerDieker syndrome; Olson and
Walsh, 2002
; Reiner et al.,
1993
), the putative microtubule motor regulator Klar
(Mosley-Bishop et al., 1999
;
Welte et al., 1998
), and the
nuclear lamin Lam DM(0) (Patterson et al.,
2004
). These studies have demonstrated that the location of the
photoreceptor nucleus depends on factors associated with the microtubule
cytoskeleton. However, it is essential to determine whether such nuclear
relocation reflects nuclear mispositioning within the cell or migration of the
entire cell, and whether the defect is simply a secondary consequence of
earlier disruptions in mitosis or alterations in the overall apical/basal
polarity of the retinal epithelium. The many molecular and genetic tools
available in the Drosophila retina facilitate the critical
examination of these issues.
The Dynactin complex is an assembly of 11 different subunits that functions
as an activator of Dynein (Gill et al.,
1991), serving as an adaptor for cargo (Holleran et al.,
1996
,
2001
;
Muresan et al., 2001
) and
enhancing motor processivity (King and
Schroer, 2000
). The Dynactin subunit Glued couples Dynactin to
Dynein by binding to the Dynein intermediate chain (Dic)
(Karki and Holzbaur, 1995
;
Vaughan and Vallee, 1995
).
Overexpression of a truncated form of Glued that binds to Dic but cannot
associate with the rest of the Dynactin complex acts as a powerful inhibitor
of Dynein and Dynactin function (Allen et
al., 1999
; Eaton et al.,
2002
; Fan and Ready,
1997
). Overexpression of the Dynactin subunit Dynamitin disrupts
Dynactin complex assembly and also inhibits Dynactin function
(Echeverri et al., 1996
;
Eckley et al., 1999
).
Biochemical studies have shown that the Dynactin complex also contains Capping
Protein (Schafer et al.,
1994
), a heterodimer composed of the Capping Protein alpha (Cpa)
and Capping Protein beta (Cpb) subunits
(Cooper et al., 1999
). Although
best known for capping the barbed ends of filaments of actin, Capping Protein
also associates with filaments of the actin-related Arp1 protein, which is a
central element of the Dynactin complex
(Cooper et al., 1999
;
Schafer et al., 1996
).
In this work we demonstrate, using multiple independent strategies to disrupt Dynactin function, that the Dynactin complex is critical for photoreceptor nuclear positioning and that Dynactin inhibition causes photoreceptor nuclei to leave the retina and move toward the brain. We show that Dynactin acts in postmitotic photoreceptors and that the disruption in nuclear positioning observed reflects the movement of the nucleus within the neuron rather than photoreceptor migration. We isolate loss-of-function mutations in kinesin heavy chain (khc) as strong suppressors of nuclear mispositioning in Glued1 mutants, and we demonstrate that Kinesin antagonizes Glued function in positioning the nuclei of postmitotic photoreceptors, both in the adult eye and in the larval photosensory organ. Our data demonstrate that the maintenance of photoreceptor nuclear position relies on Dynactin activity and suggest that the positioning of photoreceptor nuclei depends on the antagonistic activities of plus-end and minus-end directed microtubule motors.
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Materials and methods |
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cpbF44 was recovered from approximately 4400 lines of
EMS-mutagenized FRT40A flies screened for failure to complement
cpbM143 lethality. Both cpbM143 and
cpbF44 were sequenced and contained a G to A transition
introducing a stop codon after amino acid 147 of Cpb.
cpbM143 and cpbF44 were independently
induced as 14 sequence differences were detected between
cpbM143 and cpbF44 within the Cpb
transcription unit (flanking the truncation mutation); all
cpbF44 polymorphisms were shared with the FRT40A
stock used for mutagenesis. cpbM143 was generated in the
lab of E. Wieschaus. Df(2L)E.2 was provided by M. Welte. DNA from
homozygous Df(2L)E.2 embyros was examined by PCR using multiple
primer pairs covering the entire Cpb transcription unit; no Cpb DNA was
detected in these animals, suggesting Df(2L)E.2 deletes Cpb.
UAS-Gl84 was provided by G. Davis, and UAS-Nod:LacZ
by S. Thor. Homozygous mutant visual system clones were produced using the
eyeless-FLP system (Newsome et al.,
2000
).
pUAS:Cpb contains a full-length Cpb cDNA (SD07714, Research Genetics)
cloned into pUAST (Brand and Perrimon,
1993). pGlass38-1:Gal4 contains 38-1, a pentamer of a 38 bp
glass-responsive fragment from the Rh1 enhancer upstream of an hsp70 minimal
promoter (Ellis et al., 1993
),
cloned into pGATb (Brand and Perrimon,
1993
). Transgenic flies were created as described
(Spradling and Rubin, 1982
).
pGlass38-1:Gal4 drove expression in the anticipated pattern
(Ellis et al., 1993
), with
expression initiating in photoreceptors seven to eight rows behind the onset
of detectable Elav expression. As one row of ommatidia is added every 90
minutes (Wolff and Ready,
1993
) and photoreceptor axons reach the brain four to five rows
after initiation of Elav expression, the onset of detectable transgene
expression lags photoreceptor axon innervation of the target by
3 hours.
Rescue was obtained by crossing Df(2L)E.2,
Bc/+;tubulin:GAL4,UAS:mCD8GFP/+ males to p{w+,UAS:cpb},
cpbM143/SM6:TM6b,Tb virgins. A total of 235
third-instar progeny were scored for UAS:Cpb transgene rescue of cpb
lethality. All 37 cpb/Df(2L)E.2 larvae (Bc, non-Tb
larvae) were GFP-positive and thus contained both the Gal4 driver and UAS:Cpb;
no GFP-negative cpb/Df(2L)E.2 larvae, which did not contain the Gal4
driver, were recovered. Single-cell analysis in
Fig. 2 was performed by
crossing hsFLP-Actin-FRT-FRT-GAL4,UAS:GFP/Y males to w; c-s or
Gl1/TM6b virgins. Progeny were heat-shocked at 38°C
for 1 hour each day.
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Results |
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To confirm that the cpbM143 mutant photoreceptor defect
was due to a loss of cpb function, we isolated an additional strong
loss-of-function cpb allele, cpbF44, from an EMS
mutagenesis and obtained a chromosomal deficiency uncovering the cpb
locus, Df(2L)E.2 (see Materials and methods for details). When
animals contained homozygous mutant clones of cpbF44 cells
or homozygous mutant clones of Df(2L)E.2, a similar movement of
photoreceptor nuclear regions toward the brain was observed
(Fig. 1E and data not shown).
cpb/Df(2L)E.2 animals did not survive to third instar, preventing the
classic genetic demonstration that these cpb alleles behaved as
strong loss-of-function mutations. Fortunately, we found that the
[pYES-ß] genomic transgene, which contains the CPB coding region
(Hopmann et al., 1996), was
able to rescue the lethality of cpb/Df(2L)E.2 animals, but did not
rescue the previously described cpb bristle defect
(Hopmann et al., 1996
). This
suggested that [pYES-ß] was a partially functional rescue construct that
could be used to examine the visual systems of otherwise
cpb/Df(2L)E.2 animals. We found that
[pYES-ß];cpbM143/Df(2L)E.2 animals displayed a
photoreceptor defect similar to that of other cpb mutants, consistent
with nuclear mispositioning resulting from the loss of cpb function
(Fig. 1F). We further confirmed
that the defect was due to the loss of cpb function by successfully
rescuing the cpbM143/Df(2L)E.2 photoreceptor defects (as
well as the cpb bristle defects) by expression of a wild-type Cpb
cDNA under the control of a heterologous promoter
(Fig. 1G and data not shown).
Staining of photoreceptor nuclei directly demonstrated the movement of
photoreceptor nuclei out of the eye disc and into the optic stalk in
cpb mutants (Fig.
1H-J).
The bifunctional nature of Cpb, which associates with filaments of actin as
well as filaments of Arp1, means that loss of Cpb also increases filamentous
actin levels (Hopmann and Miller,
2003). Nonetheless, previous studies have shown that increases in
filamentous actin alone, such as those observed in hypomorphic cpb
alleles or in actup mutants, do not cause photoreceptor nuclear
mispositioning (Benlali et al.,
2000
; Hopmann and Miller,
2003
). Together with the Glued1 and Dynamitin
data, the cpb observations yield a consistent picture that
alterations in Dynactin subunits cause mispositioning of photoreceptor cell
bodies and nuclei, and indicate that Dynactin, and not just the Glued subunit,
has an important role in photoreceptor development.
Dynactin is required for maintenance of nuclear positioning within postmitotic photoreceptors
The mispositioning of photoreceptor nuclei in Dynactin mutants raised the
question of whether these disruptions reflect altered positioning of the
nucleus within the photoreceptor or simply migration of the entire
photoreceptor. To address this question, single photoreceptors were labeled in
wild type and in Glued1 mutants. Wild-type photoreceptors
exhibit a highly polarized morphology in which the region of the photoreceptor
containing the nucleus lies in the apical region of the eye disc and an axon
extends basally into the brain (Fig.
2A-D). Glued1 mutant photoreceptors whose
nuclei have entered the optic stalk had highly altered morphologies, with both
leading and trailing processes extending from the regions of the cell where
the misplaced nucleus was located (Fig.
2E-K). We quantified leading and trailing processes of misplaced
Glued1 photoreceptors, considering only those with no
other labeled cells or processes nearby. Of these 13 neurons, 12 had clearly
detectable leading and trailing processes. The leading process (axon) extended
into the target region and the trailing process extended back into the eye
disc. These data demonstrate that inhibition of Dynactin function dramatically
alters the position of the nucleus within the photoreceptor.
The Dynactin complex also controls the pattern of mitoses within the
Drosophila retina (Fan and Ready,
1997). To determine whether nuclear mispositioning is a secondary
consequence of the earlier mitotic requirement for Dynactin, we examined the
effects of specifically inhibiting the Dynactin complex in postmitotic
photoreceptors. Conditional inhibition of Dynactin function can be achieved
through inducible expression of a truncated, dominant-negative form Glued
(GluedDN) that resembles the protein product of
Glued1 (Allen et al.,
1999
; Fan and Ready,
1997
). GluedDN was expressed under the control of the
postmitotic photoreceptor-specific Glass 38-1 promoter, which initiates
expression in the photoreceptors only after their axons have entered the brain
(see Materials and methods). Expression of GluedDN under the
control of Glass 38-1 caused photoreceptor nuclei to move into the optic stalk
(Fig. 3A,B). Overexpression of
Dynamitin under the control of Glass 38-1 caused similar photoreceptor nuclear
positioning defects (Fig. 3C).
These data demonstrate that Dynactin is required postmitotically in
photoreceptors to maintain nuclear position and that the disruptions in
nuclear positioning observed are not simply a secondary consequence of mitotic
defects.
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Glued cooperates with Dynein in photoreceptor nuclear positioning but is antagonized by Kinesin
Dynactin activates the microtubule motor Dynein, and strong
loss-of-function mutations in dynein intermediate chain
(dic) are dominant enhancers of the rough eye phenotype of
Glued1 mutants (Boylan
and Hays, 2002). As Dynein and Dynactin may play multiple roles
together during eye development, we examined the effect of a reduction in
dic gene dosage upon photoreceptor nuclear positioning in
Glued1 animals. A twofold reduction in dic gene
dosage caused a further decrease in the number of photoreceptor nuclei in
apical regions of Glued1 mutant eye discs
(Fig. 5A,B). This did not
reflect a simple reduction in the number of photoreceptors generated, as large
numbers of photoreceptor nuclei were crowded at the base of the eye disc and
entered the optic stalk in both animals
(Fig. 5C,D). Thus, a larger
fraction of photoreceptor nuclei left apical positions when the level of
dic gene activity was reduced, consistent with Dynein and Dynactin
acting together in this process.
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Glued and Kinesin Heavy Chain also act antagonistically in positioning Bolwig photoreceptor nuclei
We examined the interaction between Glued and khc in
other photoreceptors by examining the Bolwig organ, a cluster of 12
photosensitive neurons that differentiate during embryonic development and
extend axons into the brain (Schmucker et
al., 1997). By second and third instar larval stages, Bolwig
photoreceptor nuclei are located near the anterior tip of the larva and their
axons extend over the eye/antennal disc into the brain, a distance of >200
µm. In wild-type second instar animals, photoreceptor neuron
differentiation has not yet begun in the eye disc and no neuronal nuclei are
present there (Fig. 7A).
However, when GluedDN was expressed in postmitotic Bolwig
photoreceptors, their nuclei appeared on the surface of the eye/antennal disc
(Fig. 7B,C). Thus, as in the
photoreceptors of the adult eye, expression of GluedDN in Bolwig
photoreceptors caused their nuclei to be positioned closer to their axon
termini; in many cases, the Bolwig nuclei were over 150 µm closer than
normal to their axon terminals in the brain.
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Discussion |
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Glued acts in postmitotic photoreceptors to control nuclear positioning
Establishing and maintaining appropriate nuclear position is a general
challenge for eukaryotic cells and the mechanisms that control nuclear
positioning vary with cell type and developmental stage
(Morris, 2003;
Starr and Han, 2003
). In
neurons, the position of the nucleus is initially established at the end of
the precursor cell's mitosis and changes as the neuron migrates into position
and acquires its differentiated morphology. Thus, nuclear positioning is a
dynamic process integrated into the differentiation program of a neuron.
Several alternative models have been proposed for the role of the Dynactin
subunit Glued in neuronal positioning in the fly eye
(Fan and Ready, 1997). As
Glued1 mutations affect both mitosis and nuclear
positioning in the eye, it has been difficult to assess whether Glued activity
is required specifically in postmitotic neurons. In fact, broad expression of
the cell-cycle inhibitor p21 behind the morphogenetic furrow (the region in
which photoreceptors differentiate) partially suppressed the
Glued1 nuclear positioning defect, suggesting that
disruptions in Dynactin might lead to a nuclear positioning defect by simply
disrupting the coordination of cell-cycle progression and nuclear movement
(Fan and Ready, 1997
). Our
results demonstrate that Dynactin activity is required within the postmitotic
photoreceptor to regulate nuclear positioning. We also see nuclear
mispositioning when Glued function is inhibited in postmitotic photoreceptors
of the Bolwig organ, indicating that this function is not specific for
photoreceptors generated in the eye disc.
Our analysis has focused on the positioning of the nucleus within the photoreceptor neuron. It is interesting to consider whether other constituents of the cell body are similarly mispositioned when Dynactin function is disrupted. Our analysis of single Glued1 photoreceptors indicates that mispositioned nuclei are surrounded by a concentration of other cellular material, as evidenced by the accumulation of CD8:GFP (a transmembrane protein associated with cell surfaces as well as secretory vesicles) around the nuclei in Fig. 2H,I. Thus it is possible that not only nuclei, but also other elements of the cell body, are mispositioned in these animals.
Kinesin exerts an antagonistic influence on photoreceptor nuclear positioning
Our finding that Glued collaborates with Dynein in photoreceptor neuron
nuclear positioning raises the question of whether other motor proteins
contribute to this process. From a screen for genes that promote or antagonize
Glued function in the retina, we identified loss-of-function alleles
of kinesin heavy chain (khc) and demonstrated that a
reduction in khc dosage reduced the amount of photoreceptor nuclear
mispositioning observed in Glued1 animals. These data
suggest that nuclear mispositioning does not result simply from the poisoning
of axonal transport, as a decrease in khc function exacerbates the
axonal transport defects of Glued1 animals
(Martin et al., 1999).
Furthermore, the observation of a Glued/khc interaction in
postmitotic photoreceptors of the adult eye and the larval Bolwig organ
indicates that the interplay between Glued and Kinesin occurs within the
differentiating photoreceptor. Taken together, our data suggest that the two
may normally play antagonistic roles in positioning the photoreceptor nucleus.
The fact that strong photoreceptor nuclear mispositioning is not observed in
animals containing homozygous mutant clones of khc tissue in the
retina (Brendza et al., 2000
)
(J.L.W. and P.A.G., unpublished) is perhaps not surprising, as the nucleus
normally resides near the apical surface of the retina and adjacent to the
focus of microtubule minus ends, leaving little room for further apical
movement. While the microtubule motor proteins Dynein and Kinesin are
important for nuclear positioning in many cell types
(Cottingham and Hoyt, 1997
;
DeZwaan et al., 1997
;
Duncan and Warrior, 2002
;
Januschke et al., 2002
;
Morris, 2003
;
Reinsch and Gonczy, 1998
;
Requena et al., 2001
), a role
for microtubule motors in nuclear positioning in postmitotic neurons has not
been previously established.
Roles of Dynein, Dynactin and Kinesin in photoreceptor nuclear positioning
Dynein and Dynactin control a number of cellular processes through their
effects on the structure of the microtubule cytoskeleton and through the
transportation of cargo along microtubules. In particular, Dynein and Dynactin
regulate nuclear positioning in many dividing and migrating eukaryotic cells
(Morris, 2003;
Reinsch and Gonczy, 1998
). How
do Dynein and Dynactin control photoreceptor nuclear position and how might
Kinesin exert an antagonistic influence? One possibility is that the
photoreceptor nucleus may be a cargo moved directly by the Dynein/Dynactin
complex. The proximity of the photoreceptor nucleus to the focus of
microtubule minus ends in wild-type animals would be consistent with Dynein
and Dynactin working to move the nucleus toward the focus of microtubule minus
ends, while the antagonistic interaction between Dynactin and Kinesin could
reflect the direct coupling of the nucleus to both minus-end and plus-end
directed motors. Thus, the position of the photoreceptor nucleus would reflect
the relative balance of opposing motor activities, with Dynein predominating
under normal circumstances in the photoreceptors. Such coupling to
opposite-polarity microtubule motors has been implicated in the movement of
other organelles, such as mitochondria and lipid droplets
(Gross, 2003
). This scenario
would be consistent with the movement of the photoreceptor nucleus away from
the focus of microtubule minus ends in animals mutant for klar, a
gene implicated in the coordination of plus- and minus-end directed motors
attached to lipid droplets in the Drosophila embryo
(Mosley-Bishop et al., 1999
;
Welte et al., 1998
). Although
the mechanism by which Klar may regulate microtubule motors is unknown,
klar genetically interacts with the nuclear lamin Lam DM(0)
(Patterson et al., 2004
),
raising the possibility that Klar could be involved in the coordination of
Dynein and Kinesin motors associated with the photoreceptor nuclear
envelope.
Alternatively, Dynein and Dynactin could also play more indirect roles in
photoreceptor nuclear positioning. For example, in non-motile interphase
mammalian tissue culture cells, Dynactin co-localizes with the focus of
microtubule minus ends and Dynactin disruption defocuses these minus ends
(Quintyne et al., 1999). Since
the photoreceptor nucleus normally lies adjacent to the focus of microtubule
minus ends, it is possible that nuclear movement could then be a secondary
consequence of microtubule minus-end redistribution. Such redistribution could
potentially be dependent upon Kinesin activity. In C. elegans
embryos, zyg-12 is required for close association of the nucleus with
the focus of microtubule minus ends and the ZYG-12 protein may act as a
physical link between Dynein and the nuclear envelope
(Malone et al., 2003
).
However, no functional equivalent of ZYG-12 has been identified in
Drosophila. While ZYG-12 has homology to the Hook family of proteins,
analysis of Drosophila hook indicates that it is involved in
regulating secretory and endocytic pathways rather than photoreceptor nuclear
localization (Walenta et al.,
2001
). In a similar model, Dynein and Dynactin could also control
the apical/basal positioning of the focus of microtubule minus ends. In
Saccharomyces cerevisiae, Dynein associated with the cell cortex is
postulated to control the movement of microtubules along the interior surface
of the cell (Lee et al.,
2003
). In photoreceptors, association of Dynein with the apical
cortex of the cell might act similarly to move microtubule minus ends toward
the apical tip of the photoreceptor.
To begin to test the effect of Dynactin inhibition on factors associated with the microtubule cytoskeleton, we have examined the distribution of the fusion protein, Nod:LacZ, which colocalizes with microtubule minus ends in wild-type animals. We see a strong delocalization of Nod:LacZ in Glued mutants (Fig. 4) and in cpb mutants (J.L.W. and P.A.G., unpublished). The movement of Nod:LacZ into the axon would be consistent with a defocusing of microtubule minus ends and even alterations in the overall polarity of the microtubule cytoskeleton. Such microtubule disorganization would cause Nod:LacZ to no longer travel to a single destination in Glued1 mutants. However, an alternative explanation is that Dynactin is required for the movement of Nod:LacZ to microtubule minus ends. In this scenario, Nod:LacZ would not necessarily be localized at minus ends and thus no longer serve as an effective microtubule minus-end marker in Glued1 mutants. It is interesting to note that despite the strong effects of reducing the gene dosage of dic and khc on nuclear mispositioning in GluedDN mutants, we did not see detectable effects of reducing dic or khc gene dosage on Nod:LacZ distribution in GluedDN animals (J.L.W. and P.A.G., unpublished). Thus the redistribution of Nod:LacZ may be unrelated to the mispositioning of the photoreceptor nucleus, although only a dramatic alteration in the distribution of Nod:LacZ would be detected in our assay. A more detailed analysis of microtubule organization in photoreceptors with disruptions in Dynactin functions awaits the development of additional tools.
How the distinct regions of a neuron (the axons, dendrites and nucleus-containing cell body) are properly positioned is a central question in neuronal cell biology, about which little is known. Here we have shown that Dynein and Dynactin play a major role in maintaining the position of the nucleus within a postmitotic photoreceptor neuron, and that Kinesin can antagonize this function. It will be of interest to determine whether Dynactin may be directly involved in coupling the apical/basal polarity of the photoreceptor neuron to the polarity of the microtubule cytoskeleton; for example, through association with factors involved in apical/basal polarization of the photoreceptor. Another key issue for the future is to determine whether these effects of Dynein, Dynactin and Kinesin on photoreceptor nuclear migration reflect their association with the photoreceptor nucleus and/or the effects of these complexes on the microtubule cytoskeleton more generally.
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ACKNOWLEDGMENTS |
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