1 Department of Anatomy and Developmental Biology, University College London,
Gower Street, London WC1E 6BT, UK
2 Millennium Nucleus on Integrative Neurosciences, Instituto de Ciencias
Biomedicas, Facultad de Medicina, Universidad de Chile, PO Box 70079, Santiago
7, Chile
3 Department of Developmental Biology, National Institute for Basic Biology, 38
Nishigonaka, Myodaiji, Okazaki, 444-8585, Japan
* Author for correspondence (e-mail: m.tada{at}ucl.ac.uk)
Accepted 29 April 2003
![]() |
SUMMARY |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: Wnt signalling, Planar cell polarity, Convergent extension, Gastrulation, Neuronal migration, Zebrafish
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Recent functional studies in Xenopus and genetic analyses of
gastrulation mutants in zebrafish have revealed that a noncanonical Wnt
pathway is involved in the regulation of CE. This pathway is related to the
planar cell polarity (PCP) pathway that mediates the establishment of cell
polarity in the plane of epithelia in Drosophila (reviewed in
Adler, 2002;
Mlodzik, 2002
;
Tada et al., 2002
;
Wallingford et al., 2002a
). In
vertebrates, the secreted glycoproteins Wnt11/Silberblick (Slb) and
Wnt5/Pipetail (Ppt) act as ligands
(Heisenberg et al., 2000
;
Rauch et al., 1997
;
Tada and Smith, 2000
),
although a Wnt ligand mediating PCP has yet to be found in
Drosophila. Shared components of these pathways include: Fz
receptors; an intracellular signal transducer, Dsh; a 4-pass transmembrane
protein, Van gogh/Strabismus/Trilobite (Vang/Stbm/Tri); small GTPases RhoA and
Cdc42; and a RhoA effector, Rho kinase 2
(Darken et al., 2002
;
Djiane et al., 2000
;
Goto and Keller, 2002
;
Habas et al., 2001
;
Heisenberg et al., 2000
;
Jessen et al., 2002
;
Marlow et al., 2002
;
Park and Moon, 2002
;
Tada and Smith, 2000
;
Wallingford et al., 2000
). In
vertebrates, a formin-like protein, Daam1, functions between Dsh and RhoA to
regulate the actin cytoskeleton (Habas et
al., 2001
). Moreover, downstream of the small GTPases, the
activation of Jun-N-terminal kinase (JNK) appears to be required for proper CE
movements in vertebrates and for establishing PCP in Droshophila
ommatidia (Park and Moon,
2002
; Yamanaka et al.,
2002
) (reviewed in Mlodzik,
1999
).
prickle (pk) is one of a core group of PCP genes that
controls planar polarity in the eye, leg and wing of Drosophila
(Gubb et al., 1999).
pk encodes an intracellular protein containing three LIM domains and
a conserved `PET' domain (for Prickle, Espinas and Testin). Epistasis analyses
have demonstrated that Pk is required for some aspects of Fz/Dsh-mediated PCP
signalling, but is not placed in a linear cascade with Fz and Dsh. Recent
studies indicate that Pk regulates the subcellular distribution of Fz through
binding to Dsh, thereby localising the Fz/Dsh complex to one side of the
epithelial cells (Tree et al.,
2002
).
Recently, it has become evident that genes involved in CE may also be
involved in mediating cell migration in the CNS. For instance, the PCP gene
stbm/tri is required not only during CE, but also for proper
migration of branchiomotor neurons (Bingham
et al., 2002; Jessen et al.,
2002
). This raises the intriguing possibility that vertebrate
homologues of other PCP genes might participate in the regulation of CE
movements as well as during neuronal migration.
In this study, we analyse the function of a zebrafish homologue of the Drosophila PCP gene pk during gastrulation and neuronal migration. Zebrafish pk1 is expressed in moving mesodermal cells and overlying neuroectodermal cells during gastrulation, and functions together with Slb/Wnt11 and Ppt/Wnt5 to regulate CE movements in both mesendoderm and ectoderm. Possibly analogous to its role in flies, we find that Pk1 can destabilise Dsh and thereby block the ability of Fz to target Dsh to the cell membrane. In addition to its role in CE, pk1 also mediates the migration of cranial motor neurons and shows a strong genetic interaction with Tri in this process. These results show that Pk1 modulates different types of cell behaviour during CE and neuronal migration.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Cloning of zebrafish pk
Est sequence highly homologous to Xenopus pk (M. T. and N.U.,
unpublished) was used to design primers for RT-PCR from zebrafish gastrula
embryos. The isolated fragment was used to screen a zebrafish-shield library
(kindly provided by Michael Rebagliati) to isolate a full-length cDNA for
zebrafish pk1. The accession number of pk1 is AY286492. For
injection studies, the coding region of pk1 was cloned into
pCS2+.
In situ hybridisation
Antisense RNA probes were produced with a digoxygenin RNA-labelling kit
(Boehringer Mannheim) according to the manufacturer's instructions using
plasmids containing cDNA for pk1 (this study), ntl
(Schulte-Merker et al., 1994),
hgg1 (Thisse et al.,
1994
), dlx3 (Akimenko
et al., 1994
), papc
(Yamamoto et al., 1998
),
myoD (Weinberg et al.,
1996
), emx1 (Morita
et al., 1995
), rx3
(Chuang et al., 1999
),
pax2.1 (Krauss et al.,
1991
), chordino (chd)
(Schulte-Merker et al., 1997
),
bmp2b (Nikaido et al.,
1997
), sna2 (Thisse
et al., 1995
) and krox20
(Oxtoby and Jowett, 1993
).
Whole mount, in situ hybridisation was performed essentially as previously
described (Barth and Wilson,
1995
). Expression of GFP was detected using an anti-GFP polyclonal
antibody (AMS Biotechnology), essentially as described previously
(Shanmugalingam et al.,
2000
).
RNA and morpholino antisense oligonucleotide (Mo) injection
RNAs encoding zebrafish Wnt11
(Heisenberg et al., 2000),
zebrafish Fz7 (El-Messaoudi and Renucci,
2001
), Xenopus Dsh-GFP
(Rothbacher et al., 2000
) and
Pk1 were synthesised essentially as described
(Smith, 1993
). All injections
were performed on one-cell-stage embryos.
A Mo against pk1 (pk1-Mo) was designed over the initiation methionine of Pk1: 5'-GCCCACCGTGATTCTCCAGCTCCAT-3'. A control Mo including four mismatched nucleotides [underlined, pk1-Mo (Mis)] is as follows: 5'-GCCCGCCATGATTCTCCAACTTCAT-3'. Injection of the control Mo in wild-type embryos causes no defective phenotype (data not shown). The specificity of pk1-Mo was determined by co-injection of RNA encoding GFP-tagged with amino acid sequences that include sequence corresponding to the pk1-Mo but not pk1-Mo (Mis). pk1-Mo but not pk1-Mo (Mis) prevented production of GFP (data not shown).
Cell transplantation
For transplantations, donor embryos were injected with either
rhodamine-dextran (MW 10,000, Molecular probe) plus 5 pg pk1 RNA or
fluorescein-dextran (MW 10,000, Molecular probe) at the one-cell stage. Cells
were taken from late-blastula host embryos and transplanted into deep regions
of the germ ring of host wild-type embryos as described previously
(Heisenberg et al., 2000).
Tailbud-staged embryos were mounted in 1.5% methylcellulose and image analysis
was performed using Openlab software.
Analyses for sub-cellular protein localisation
To monitor Dsh localisation, embryos at the one-cell stage were injected
with 200 pg RNA encoding Dsh-GFP either with or without 50 pg fz7 RNA
and either with or without 5 pg pk1 RNA and were mounted in 1%
agarose at 40% epiboly. Image analysis of living embryos was carried out using
a Leica DMLFS confocal microscope with a 63x water-immersion lens. We
were unable to monitor Pk1 localisation in living embryos because expression
of a GFP-tagged version of Pk1, even at moderate doses caused embryos to
develop abnormally at early stages. Therefore, to analyse Pk1 localisation
embryos were injected with 25 pg of RNA encoding Venus-Pk1 (Venus is an
EYFP-derivative that was kindly provided by Atsushi Miyawaki) and fixed at 40%
epiboly for anti-GFP antibody staining.
Western-blot analysis
To monitor the levels of Dsh protein, embryos were injected with 200 pg RNA
encoding myc-Dsh either with or without 50 pg fz7 RNA and either with
or without 5 pg pk1 RNA at the one-cell stage. Blastoderms from 20
embryos at 40% epiboly were collected for western-blot analysis after removal
of the yolk according to a protocol kindly provided by Carl-Philipp Heisenberg
(personal communication). Protein from the equivalent of five blastoderms was
subject to SDS-PAGE (8% acrylamide gel) and then blotted to a PVDF membrane
(Amersham). The membrane was reacted with 9E10 anti-myc monoclonal antibody
(Santa Cruz Biotechnology) and subsequently with anti-mouse IgG conjugated
with HRP followed by detection with ECL (Amersham). For loading control, the
membrane was counter-stained with anti-ß-tubulin monoclonal antibody
(Sigma) and visualised with NBT and BCIP.
A planar polarity gene pk1 is expressed maternally and in
moving mesodermal precursors
To investigate whether homologues of the Drosophila PCP gene
pk function during vertebrate gastrulation, we isolated a full-length
clone of a zebrafish pk gene from a shield library. The predicted
protein encoded by zebrafish pk1 shares 85% and 82% amino acid
identity to Xenopus XPk-A
(Wallingford et al., 2002b) in
a highly conserved PET domain of unknown function and three LIM domains,
respectively (Fig. 1A).
Phylogenetic analysis on the basis of the conserved PET and LIM domains shows
zebrafish pk1 is more closely related to Drosophila pk and
espinas than to another closely related gene testin (data
not shown).
|
Interfering with Pk1 function disrupts CE during gastrulation
To analyse the function of Pk1, we first employed an antisense approach
using morpholino oligonucleotides against pk1 (pk1-Mo) to
reduce the level of endogenous Pk1 protein
(Nasevicius and Ekker, 2000).
Injection of 3 ng pk1-Mo led to a shorter body axis with a curled
down tail at pharyngula stage (99%, n>500)
(Fig. 2A,B). At higher doses,
injected embryos exhibited a more severe phenotype with shorter trunk and
tail, but occasionally this was associated with cell death in the brain at
later stages (data not shown). Thereafter, we used a moderate dose (3 ng) for
further analyses of the pk1 morphant phenotype.
|
Pk1 regulates CE movements by modulating the Wnt/PCP pathway
The CE phenotype caused by interfering with Pk1 function is similar to
those in slb/wnt11 and ppt/wnt5 loss-of-function mutants
(Heisenberg et al., 2000;
Kilian et al., 2003
;
Rauch et al., 1997
). In
Drosophila, pk genetically interacts with the Fz/PCP pathway to
establish epithelial polarity (Gubb et
al., 1999
). This led us to test the possibility that vertebrate Pk
regulates CE through interaction with the Wnt/PCP pathway. First, we tested if
there was any genetic interaction between slb and pk1.
Injection of pk1-Mo in slb embryos enhanced the CE defect
compared to either mutant/morphant alone, with the consequence that the
prechordal plate remained posteriorly located beneath the neural plate (50%,
n=92) (Fig. 3A,B).
This result indicated that Pk1 may function in the Wnt/PCP pathway or in
parallel to this pathway.
|
Because ppt/wnt5 is expressed in similar domains to pk1,
is required for CE movements in the posterior region of the gastrula, and
genetically interacts with slb/wnt11
(Kilian et al., 2003), we
examined whether Pk1 also modulates the activity of Ppt. Both
ppt-/- embryos and pk1 morphants have a shorter
body axis (Fig. 4A,C,E), in
which somites are wider and thinner when compared to wild-type
(Fig. 4B,D,F).
ppt/wnt5 mutant embryos with reduced Pk1 function showed a phenotype
much more severe than either single mutant/morphant with greatly compressed
wider somites (42%, n=118) (Fig.
4G,H), indicating that Ppt and Pk1 function redundantly in
regulating CE in the posterior region.
|
Gain-of-function of pk1 causes defective CE movements by
modulating the Wnt/PCP pathway
To complement our analysis of cell movements in embryos with reduced Pk1
activity, we investigated the consequences of increased levels of Pk1.
Ubiquitous over-expression of pk1 RNA, even at low dose (5 pg),
caused abnormal cell aggregation at blastula stages precluding analysis of
cell migration during gastrulation (data not shown). To overcome these early
defects, we assayed the behaviour of small groups of cells over-expressing Pk1
in a wild-type environment. To achieve this, differentially labelled wild-type
and Pk1-overexpressing cells were transplanted into the germ rings of
wild-type host embryos (Fig.
5A). Following transplantation, convergence and extension
movements redistribute the wild-type cells along the antero-posterior axis by
tailbud stage (Fig. 5B)
(Heisenberg et al., 2000). In
comparison to wild-type, cells overexpressing Pk1 show less dorsal convergence
and less spread along the antero-posterior axis (70%, n=40)
(Fig. 5B). This indicates that
elevated Pk1 activity inhibits cells from undergoing proper gastrulation
movements.
|
Next, we attempted to assay if Pk1 modulates the Wnt/PCP pathway by
regulating the subcellular localisation of components of this pathway. In the
Drosophila wing, asymmetric localisation of the Fz-Dsh complex at the
distal edge of each cell determines cell polarity within the plane of the
epithelia (Axelrod, 2001;
Strutt, 2001
). During this
process, Pk regulates localisation of Fz/Dsh by inhibiting the complex from
forming at the proximal edges of the cells
(Tree et al., 2002
). In
vertebrates, membrane localisation of Dsh in cells undergoing CE
(Wallingford et al., 2000
) is
dependent on Fz (Axelrod et al.,
1998
; Rothbacher et al.,
2000
; Umbhauer et al.,
2000
). Therefore, we examined whether Pk1 affects the localisation
of the Fz/Dsh complex in zebrafish embryos. When Dsh-GFP is expressed in
animal pole blastomeres, it predominantly localises to the cytoplasm,
sometimes associated with vesicles-like structures (100%, n=10)
(Fig. 5F). This presumably
reflects the requirement of Dsh to localise to vesicles for canonical Wnt
signalling (Capelluto et al.,
2002
). In response to Fz7, Dsh is targeted to the membrane (90%,
n=30) (Fig. 5G), but
this is inhibited by increasing Pk1 activity (100%, n=21)
(Fig. 5H). The predominantly
cytoplasmic localisation of Pk1 (Fig.
5I) remains unchanged in the presence of Fz7 (data not shown).
These observations, together with the fact that cytoplasmic Dsh-GFP becomes
faint and hazy when Pk activity is increased
(Fig. 5H), raised the
possibility that Pk1 activity may destabilise Dsh, thereby blocking
Fz7-mediated membrane localisation of Dsh.
To test if Pk1 affects the levels of Dsh protein, we quantified myc-tagged Dsh in the presence of Fz7 with or without Pk1. Western blot analysis revealed that the levels of Dsh are significantly lower in the presence of Pk1 (Fig. 5J). These data indicate that the disruption/degradation of the Fz/Dsh complex by Pk1 may contribute to the ability of exogenous Pk1 to negatively regulate the Wnt/PCP pathway.
pk1 genetically interacts with tri/stbm
The ability of Pk1 to regulate CE by modulating the Wnt/PCP pathway is
similar to that of Tri/Stbm (Jessen et
al., 2002). We therefore investigated whether there is any genetic
interaction between pk1 and tri/stbm in regulating CE
movements. In the progeny of crosses between heterozygous tri
carriers, approximately one quarter of embryos injected with 3 ng
pk1-Mo showed a more severely compressed body axis as compared to
tri homozygotes (Fig.
6A,B,G-J; Table 1).
In addition, a further half of the injected population exhibited a phenotype
indistinguishable from homozygous tri embryos. To confirm that the
tri-like phenotype arose from abrogation of Pk1 activity in
heterozygous tri+/- embryos, we injected pk1-Mo
in embryos from crosses between heterozygous tri female and wild-type
male fish. About 40% of injected embryos showed a tri-like phenotype,
more severe than wild-type embryos injected with pk1-Mo
(Fig. 6C-F,
Table 1). These results suggest
that Pk1 and Tri function in the same genetic pathway.
|
|
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
pk1 regulates CE movements by modulating the noncanonical
Wnt/PCP pathway
Our analysis of Pk1 function adds to a growing body of evidence that a
molecular pathway involving noncanonical Wnts and homologues of fly PCP genes
(Adler, 2002;
Mlodzik, 2002
) regulates cell
movements underlying CE. Although Pk1 acts together with Wnt11 and Wnt5, it is
not simply a linear component of the Wnt/PCP pathway because both loss- and
gain-of-functions of Pk1 enhance the slb mutant phenotype. Consistent
with this conclusion, in Drosophila PCP, Pk is a context-dependent
positive or negative modulator of Fz/PCP signalling, rather than just a
downstream component of the pathway (Adler
et al., 2000
; Gubb et al.,
1999
; Tree et al.,
2002
).
In the Drosophila wing, Pk inhibits the Fz/Dsh complex from
forming on the proximal edges of the epithelial cells, thereby functioning in
a feedback loop that amplifies differences between Fz/Dsh levels on adjacent
cells (Tree et al., 2002).
Similarly, we have shown that vertebrate Pk1 can disrupt the Fz7-dependent
membrane localisation of Dsh, despite the fact that Pk1 is neither localised
to the membrane nor recruited to the membrane by Fz-7. In addition, increasing
Pk1 activity alters the stability of exogenous Dsh. Considering that Pk binds
directly to Dsh in vitro (Tree et al.,
2002
), Pk might dissociate Dsh from the membrane to the cytoplasm
by direct binding and, subsequently, mediate the degradation of Dsh by unknown
mechanisms. Alternatively, Pk1 might destabilise Dsh at the membrane through
an indirect mechanism. In this scenario, Pk1 might co-operate with a factor at
the membrane that, in turn, binds to Dsh and leads to dissociation from
Fz.
One such candidate is the four-pass transmembrane protein Tri/Stbm/Van Gogh
(Jessen et al., 2002;
Taylor et al., 1998
;
Wolff and Rubin, 1998
). In
Drosophila stbm mutants, like pk mutants, Fz is
symmetrically localised in the membrane
(Strutt, 2001
), and
stbm interacts genetically with pk
(Taylor et al., 1998
). These
observations indicate that, in flies, Stbm functions with Pk to establish PCP.
Supporting a similar interaction in vertebrates, we show that heterozygous
tri+/- embryos injected with pk1-Mo exhibit a
tri-like phenotype. This reveals a strong genetic interaction between
pk1 and tri in the regulation of CE. Taken together with
evidence that both Stbm and Pk1 can bind to Dsh and activate JNK in cultured
cells (Park and Moon, 2002
;
Tree et al., 2002
), it seems
likely that Pk and Stbm function by similar mechanisms in the regulation of
vertebrate CE and in the establishment of PCP in Drosophila.
pk1 and tri/stbm regulate neuronal migration
independently of the Wnt/PCP pathway
In addition to disrupting CE, abrogation of Pk1 activity disrupts the
tangential migration of hindbrain branchiomotor neurons. As during CE, there
is a strong genetic interaction between Pk1 and Tri in the regulation of
neuronal migration. However, unlike in tri and pk1
mutants/morphants, branchiomotor neuron migration is unaffected by either
slb, ppt and kny mutations or by overexpression of a
dominant-negative form of Dsh which efficiently suppresses the
Wnt/PCP-mediated CE movements (Bingham et
al., 2002; Jessen et al.,
2002
). These observations raise the intriguing possibility that,
regardless of the presence or absence of Wnt/PCP pathway signalling, Pk might
act in the same molecular pathway as Tri to regulate cell behaviours that
underlie CE and tangential neuronal migration.
pk is expressed in the local environment through which the nVII
branchiomotor neurons migrate while tri is expressed more broadly in
the hindbrain (Park and Moon,
2002). It is intriguing that pk1 expression is relatively
low in r4 and r5, where the nVII neurons undergo tangentially oriented caudal
migrations, but higher in lateral regions of r6 (and more caudal rhombomeres),
where the neurons change from tangential to laterally-directed radial
migration (Chandrasekhar et al.,
1997
; Higashijima et al.,
2000
). The fact that even a subtle increase or decrease in Pk1
activity affects cell movements in pregastrula and gastrula embryos raises the
intriguing possibility that changes in Pk1 activity could influence different
aspects of neuronal movement. For instance, a low level of Pk1 between r4 and
r6 might function together with cues (e.g.
Studer, 2001
) that facilitate
tangential cell migration whereas high levels of Pk1 activity in r6 might
modulate cues that inhibit further tangential migration and/or promote radial
migration. We suggest that Pk1 might act as an intracellular sensor that
mediates attractive/repulsive cues in a manner dependent on ubiquitously
expressed Tri.
Possible interactions between genes involved in PCP/CE and neuronal
migration
How might Stbm and Pk regulate tangential migration of facial motor neurons
independent of the Wnt/PCP pathway? The Robo/Slit pathway is a candidate for
exhibiting functional interaction with Stbm/Pk. Slit guides the migration of
axons and neurons through its receptor Robo in both Drosophila and
vertebrates (Brose et al.,
1999; Hutson and Chien,
2002
; Kidd et al.,
1999
; Wu et al.,
1999
; Zhu et al.,
1999
). Indeed, in the zebrafish hindbrain, slit2 is
expressed in the midline floor plate, slit3 is expressed in
branchiomotor neurons (Yeo et al.,
2001
) and three robo genes are expressed, overlapping
with pk1, in the environment through which the nVII neurons migrate
(Lee et al., 2001
). Moreover,
overexpression studies (Yeo et al.,
2001
) indicate that Slit/Robo signalling might influence CE
movements through acting as a repulsive cue that modulates cell behaviour at
the midline of the gastrula. Indeed, as cells approach the midline they lose
bipolar protrusive activity and adopt monopolar cell morphology
(Elul and Keller, 2000
). Given
that Stbm/Pk and Slit/Robo could both be involved in the same discrete cell
migrations, it will be interesting to test the possibility that these genes
interact to influence cell behaviour.
Finally, flamingo (fmi), a core PCP gene that encodes a
seven-pass transmembrane protein with extracellular cadherin repeats, can also
function independent of Fz/Dsh signalling. Although the role of fmi
in the establishment of PCP is dependent on Fz and Dsh
(Shimada et al., 2001;
Usui et al., 1999
),
fmi also regulates dendrite outgrowth independent of the Fz/Dsh
pathway (Gao et al., 2000
).
The Fz/Dsh-dependent and independent activities of Fmi, Stbm and Pk lead us to
speculate that PCP genes might co-ordinate the behaviour of large populations
of cells in a Wnt/PCP-dependent fashion, whereas they might confer
directionality to either migration or process outgrowth of small groups of
cells independent of the Wnt/PCP pathway. As yet, there is little data on the
roles of vertebrate fmi genes and it will be interesting to determine
if they do function in the same pathways as Stbm and Pk during CE and neuronal
migration.
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
Footnotes |
---|
Moon's and Ueno's groups have also recently reported that prickle
is required for CE cell movements during gastrulation in zebrafish and
Xenopus (Veeman et al.,
2003; Takeuchi et al.,
2003
).
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Adler, P. N. (2002). Planar signaling and morphogenesis in Drosophila. Dev. Cell 2, 525-535.[Medline]
Adler, P. N., Taylor, J. and Charlton, J. (2000). The domineering nonautonomy of frizzled and van Gogh clones in the Drosophila wing is a consequence of a disruption in local signaling. Mech. Dev. 96,197 -207.[CrossRef][Medline]
Akimenko, M. A., Ekker, M., Wegner, J., Lin, W. and Westerfield, M. (1994). Combinatorial expression of three zebrafish genes related to distalless: part of a homeobox gene code for the head. J. Neurosci. 14,3475 -3486.[Abstract]
Axelrod, J. D. (2001). Unipolar membrane
association of Dishevelled mediates Frizzled planar cell polarity signaling.
Genes Dev. 15,1182
-1187.
Axelrod, J. D., Miller, J. R., Shulman, J. M., Moon, R. T. and
Perrimon, N. (1998). Differential recruitment of Dishevelled
provides signaling specificity in the planar cell polarity and Wingless
signaling pathways. Genes Dev.
12,2610
-2622.
Barth, K. A. and Wilson, S. W. (1995).
Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate
hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic
forebrain. Development
121,1755
-1768.
Bingham, S., Higashijima, S., Okamoto, H. and Chandrasekhar, A. (2002). The Zebrafish trilobite gene is essential for tangential migration of branchiomotor neurons. Dev. Biol. 242,149 -160.[CrossRef][Medline]
Brose, K., Bland, K. S., Wang, K. H., Arnott, D., Henzel, W., Goodman, C. S., Tessier-Lavigne, M. and Kidd, T. (1999). Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96,795 -806.[Medline]
Capelluto, D. G., Kutateladze, T. G., Habas, R., Finkielstein, C. V., He, X. and Overduin, M. (2002). The DIX domain targets dishevelled to actin stress fibres and vesicular membranes. Nature 419,726 -729.[CrossRef][Medline]
Chandrasekhar, A., Moens, C. B., Warren J. T., Jr, Kimmel, C. B.
and Kuwada, J. Y. (1997). Development of branchiomoter
neurons in zebrafish. Development
124,2633
-2644.
Chuang, J. C., Mathers, P. H. and Raymond, P. A. (1999). Expression of three Rx homeobox genes in embryonic and adult zebrafish. Mech. Dev. 84,195 -198.[CrossRef][Medline]
Concha, M. L. and Adams, R. J. (1998). Oriented
cell divisions and cellular morphogenesis in the zebrafish gastrula and
neurula: a time-lapse analysis. Development
125,983
-994.
Darken, R. S., Scola, A. M., Rakeman, A. S., Das, G., Mlodzik,
M. and Wilson, P. A. (2002). The planar polarity gene
strabismus regulates convergent extension movements in Xenopus.
EMBO J. 21,976
-985.
Djiane, A., Riou, J., Umbhauer, M., Boucaut, J. and Shi, D.
(2000). Role of frizzled 7 in the regulation of convergent
extension movements during gastrulation in Xenopus laevis.
Development 127,3091
-3100.
El-Messaoudi, S. and Renucci, A. (2001). Expression pattern of the frizzled 7 gene during zebrafish embryonic development. Mech. Dev. 102,231 -234.[CrossRef][Medline]
Elul, T. and Keller, R. (2000). Monopolar protrusive activity: a new morphogenic cell behavior in the neural plate dependent on vertical interactions with the mesoderm in Xenopus. Dev. Biol. 224,3 -19.[CrossRef][Medline]
Gao, F. B., Kohwi, M., Brenman, J. E., Jan, L. Y. and Jan, Y. N. (2000). Control of dendritic field formation in Drosophila: the roles of flamingo and competition between homologous neurons. Neuron 28,91 -101.[Medline]
Goto, T. and Keller, R. (2002). The planar cell polarity gene Strabismus regulates convergence and extension and neural fold closure in Xenopus. Dev. Biol. 247,165 -181.[CrossRef][Medline]
Gubb, D., Green, C., Huen, D., Coulson, D., Johnson, G., Tree,
D., Collier, S. and Roote, J. (1999). The balance between
isoforms of the prickle LIM domain protein is critical for planar polarity in
Drosophila imaginal discs. Genes Dev.
13,2315
-2327.
Habas, R., Kato, Y. and He, X. (2001). Wnt/Frizzled activation of rho regulates vertebrate gastrulation and requires a novel formin homology protein daam1. Cell 107,843 -854.[CrossRef][Medline]
Hammerschmidt, M., Pelegri, F., Mullins, M. C., Kane, D. A.,
Brand, M., van Eeden, F. J., Furutani-Seiki, M., Granato, M., Haffter, P.,
Heisenberg, C. P. et al. (1996). Mutations affecting
morphogenesis during gastrulation and tail formation in the zebrafish, Danio
rerio. Development 123,143
-151.
Heisenberg, C. P. and Nusslein-Volhard, C. (1997). The function of silberblick in the positioning of the eye anlage in the zebrafish embryo. Dev. Biol. 184, 85-94.[CrossRef][Medline]
Heisenberg, C. P., Tada, M., Rauch, G. J., Saude, L., Concha, M. L., Geisler, R., Stemple, D. L., Smith, J. C. and Wilson, S. W. (2000). Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405, 76-81.[CrossRef][Medline]
Higashijima, S., Hotta, Y. and Okamoto, H.
(2000). Visualization of cranial moter neurons in live transgenic
zebrafish expressing green fluorescent protein under the control of islet-1
promoter/enhancer. J. Neurosci.
20,206
-218.
Hutson, L. D. and Chien, C. B. (2002). Pathfinding and error correction by retinal axons: the role of astray/robo2. Neuron 33,205 -217.[Medline]
Jessen, J. R., Topczewski, J., Bingham, S., Sepich, D. S., Marlow, F., Chandrasekhar, A. and Solnica-Krezel, L. (2002). Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nat. Cell Biol. 4, 610-615.[Medline]
Keller, R., Davidson, L., Edlund, A., Elul, T., Ezin, M., Shook, D. and Skoglund, P. (2000). Mechanisms of convergence and extension by cell intercalation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 355,897 -922.[CrossRef][Medline]
Kidd, T., Bland, K. S. and Goodman, C. S. (1999). Slit is the midline repellent for the robo receptor in Drosophila. Cell 96,785 -794.[Medline]
Kilian, B., Mansukoski, H., Carreira-Barbosa, F., Tada, M. and Heisenberg, C. P. (2003). The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech. Dev. 120,467 -476.[CrossRef][Medline]
Krauss, S., Johansen, T., Korzh, V. and Fjose, A. (1991). Expression of the zebrafish paired box gene pax[zf-b] during early neurogenesis. Development 113,1193 -1206.[Abstract]
Lee, J. S., Ray, R. and Chien, C. B. (2001). Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration. Dev. Dyn. 221,216 -230.[CrossRef][Medline]
Marlow, F., Topczewski, J., Sepich, D. and Solnica-Krezel, L. (2002). Zebrafish rho kinase 2 acts downstream of wnt11 to mediate cell polarity and effective convergence and extension movements. Curr. Biol. 12,876 -884.[CrossRef][Medline]
Mlodzik, M. (1999). Planar polarity in the
Drosophila eye: a multifaceted view of signaling specificity and
cross-talk. EMBO J. 18,6873
-6879.
Mlodzik, M. (2002). Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? Trends Genet. 18,564 -571.[CrossRef][Medline]
Morita, T., Nitta, H., Kiyama, Y., Mori, H. and Mishina, M. (1995). Differential expression of two zebrafish emx homeoprotein mRNAs in the developing brain. Neurosci. Lett. 198,131 -134.[CrossRef][Medline]
Nasevicius, A. and Ekker, S. C. (2000). Effective targeted gene `knockdown' in zebrafish. Nat. Genet. 26,216 -220.[CrossRef][Medline]
Nikaido, M., Tada, M., Saji, T. and Ueno, N. (1997). Conservation of BMP signaling in zebrafish mesoderm patterning. Mech. Dev. 61, 75-88.[CrossRef][Medline]
Oxtoby, E. and Jowett, T. (1993). Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development. Nucleic Acids Res. 21,1087 -1095.[Abstract]
Park, M. and Moon, R. T. (2002). The planar cell-polarity gene stbm regulates cell behaviour and cell fate in vertebrate embryos. Nat. Cell Biol. 4, 20-25.[CrossRef][Medline]
Rauch, G. J., Hammerschmidt, H., Blader, P., Schauerte, H. E., Strahle, U., Ingham, P. W., McMahon, A. P. and Haffter, P. (1997). Wnt5 is required for tail formation in the zebrafish embryo. Cold Spring Harb. Symp. Quant. Biol. 62,227 -234.[Medline]
Rothbacher, U., Laurent, M. N., Deardorff, M. A., Klein, P. S.,
Cho, K. W. and Fraser, S. E. (2000). Dishevelled
phosphorylation, subcellular localization and multimerization regulate its
role in early embryogenesis. EMBO J.
19,1010
-1022.
Schulte-Merker, S., Hammerschmidt, H., Beuchle, D., Cho, K. W.,
De Robertis, E. M. and Nusslein-Volhard, C. (1994).
Expression of zebrafish goosecoid and no tail gene products in wild-type and
mutant no tail embryos. Development
120,843
-852.
Schulte-Merker, S., Lee, K. J., McMahon, A. P. and Hammerschmidt, M. (1997). The zebrafish organizer requires chordino. Nature 387,862 -863.[CrossRef][Medline]
Shanmugalingam, S., Houart, C., Picker, A., Reifers, F.,
Macdonald, R., Barth, A., Griffin, K., Brand, M. and Wilson, S. W.
(2000). Ace/Fgf8 is required for forebrain commissure formation
and patterning of the telencephalon. Development
127,2549
-2561.
Shih, J. and Keller, R. (1992). Cell motility
driving mediolateral intercalation in explants of Xenopus laevis.
Development 116,901
-914.
Shimada, Y., Usui, T., Yanagawa, S., Takeichi, M. and Uemura, T. (2001). Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization. Curr. Biol. 11,859 -863.[CrossRef][Medline]
Smith, J. C. (1993). Purifying and assaying mesoderm-inducing factors from vertebrate embryos. In Cellular Interactions in Development A Practical Approach, pp.181 -204. Oxford: Oxford University Press.
Solnica-Krezel, L., Stemple, D. L., Mountcastle-Shah, E.,
Rangini, Z., Neuhauss, S. C., Malicki, J., Schier, A. F., Stainier, D. Y.,
Zwartkruis, F., Abdelilah, S. et al. (1996). Mutations
affecting cell fates and cellular rearrangements during gastrulation in
zebrafish. Development
123, 67-80.
Strutt, D. I. (2001). Asymmetric localization of frizzled and the establishment of cell polarity in the Drosophila wing. Mol. Cell 7,367 -375.[Medline]
Studer, M. (2001). Initiation of facial
motoneurone migration is dependent on rhombomeres 5 and 6.
Development 128,3707
-3716.
Tada, M., Concha, M. L. and Heisenberg, C. P. (2002). Non-canonical Wnt signalling and regulation of gastrulation movements. Semin. Cell Dev. Biol. 13,251 -260.[CrossRef][Medline]
Tada, M. and Smith, J. C. (2000).
Xwnt11 is a target of Xenopus Brachyury: regulation of
gastrulation movements via Dishevelled, but not through the canonical Wnt
pathway. Development
127,2227
-2238.
Takeuchi, M., Nakabayashi, J., Sakaguchi, T., Yamamoto, T. S., Takahashi, H., Takeda, H. and Ueno, N. (2003). The prickle-related gene in vertebrates is essential for gastrulation cell movements. Curr. Biol. 13,674 -679.[CrossRef][Medline]
Taylor, J., Abramova, N., Charlton, J. and Adler, P. N.
(1998). Van Gogh: a new Drosophila tissue
polarity gene. Genetics
150,199
-210.
Thisse, C., Thisse, B., Halpern, M. E. and Postlethwait, J. H. (1994). Goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas. Dev. Biol. 164,420 -429.[CrossRef][Medline]
Thisse, C., Thisse, B. and Postlethwait, J. H. (1995). Expression of snail2, a second member of the zebrafish snail family, in cephalic mesendoderm and presumptive neural crest of wild-type and spadetail mutant embryos. Dev. Biol. 172, 86-99.[CrossRef][Medline]
Topczewski, J., Sepich, D. S., Myers, D. C., Walker, C., Amores, A., Lele, Z., Hammerschmidt, M., Postlethwait, J. and Solnica-Krezel, L. (2001). The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension. Dev. Cell 1,251 -264.[Medline]
Tree, D. R., Shulman, J. M., Rousset, R., Scott, M. P., Gubb, D. and Axelrod, J. D. (2002). Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell 109,371 -381.[Medline]
Umbhauer, M., Djiane, A., Goisset, C., Penzo-Mendez, A., Riou,
J. F., Boucaut, J. C. and Shi, D. L. (2000). The C-terminal
cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates
Wnt/beta-catenin signalling. EMBO J.
19,4944
-4954.
Usui, T., Shima, Y., Shimada, Y., Hirano, S., Burgess, R. W., Schwarz, T. L., Takeichi, M. and Uemura, T. (1999). Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98,585 -595.[Medline]
Veeman, M. T., Slusarski, D. C., Kaykas, A., Louie, S. H. and Moon, R. T. (2003). Zebrafish prickle, a modulator of noncanonical wnt/fz signaling, regulates gastrulation movements. Curr. Biol. 13,680 -685.[CrossRef][Medline]
Wallingford, J. B., Fraser, S. E. and Harland, R. M. (2002a). Convergent extension: the molecular control of polarized cell movement during embryonic development. Dev. Cell 2, 695-706.[Medline]
Wallingford, J. B., Goto, T., Keller, R. and Harland, R. M. (2002b). Cloning and expression of Xenopus Prickle, an orthologue of a Drosophila planar cell polarity gene. Mech. Dev. 116,183 -186.[CrossRef][Medline]
Wallingford, J. B., Rowning, B. A., Vogeli, K. M., Rothbacher, U., Fraser, S. E. and Harland, R. M. (2000). Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405,81 -85.[CrossRef][Medline]
Warga, R. M. and Kimmel, C. B. (1990). Cell movements during epiboly and gastrulation in zebrafish. Development 108,581 -591.[Abstract]
Weinberg, E. S., Allende, M. L., Kelly, C. S., Abdelhamid, A.,
Murakami, T., Andermann, P., Doerre, O. G., Grunwald, D. J. and Riggleman,
B. (1996). Developmental regulation of zebrafish MyoD in
wild-type, no tail and spadetail embryos. Development
122,271
-280.
Wolff, T. and Rubin, G. M. (1998).
strabismus, a novel gene that regulates tissue polarity and cell fate
decisions in Drosophila. Development
125,1149
-1159.
Wu, W., Wong, K., Chen, J., Jiang, Z., Dupuis, S., Wu, J. Y. and Rao, Y. (1999). Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 400,331 -336.[CrossRef][Medline]
Yamamoto, A., Amacher, S. L., Kim, S. H., Geissert, D., Kimmel,
C. B. and De Robertis, E. M. (1998). Zebrafish paraxial
protocadherin is a downstream target of spadetail involved in morphogenesis of
gastrula mesoderm. Development
125,3389
-3397.
Yamanaka, H., Moriguchi, T., Masuyama, N., Kusakabe, M.,
Hanafusa, H., Takada, R., Takada, S. and Nishida, E. (2002).
JNK functions in the non-canonical Wnt pathway to regulate convergent
extension movements in vertebrates. EMBO Rep.
3, 69-75.
Yeo, S. Y., Little, M. H., Yamada, T., Miyashita, T., Halloran, M. C., Kuwada, J. Y., Huh, T. L. and Okamoto, H. (2001). Overexpression of a slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish. Dev. Biol. 230,1 -17.[CrossRef][Medline]
Zhu, Y., Li, H., Zhou, L., Wu, J. Y. and Rao, Y. (1999). Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex. Neuron 23,473 -485.[Medline]