1 Department of Molecular Biology, Princeton University, Princeton, NJ 08544,
USA
2 Department of Biology, Rider University, Lawrenceville, NJ 08648, USA
Author for correspondence (e-mail:
armorris{at}haverford.edu)
Accepted 31 July 2003
![]() |
SUMMARY |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: Pronephric duct, Cell migration, Axolotl, Extracellular matrix, Cell guidance, Laminin 1, 6ß1 integrin
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The events of PND morphogenesis have been fairly well conserved during
vertebrate evolution. The PND primordium is first observed in association with
the incipient pronephros originating from lateral mesoderm located just
ventral to the developing somites at the level of the cervical vertebrae. The
PND then extends caudally along a precisely defined pathway between the
lateral and somitic mesoderm. PND elongation continues until the PND fuses
with the cloaca, the exit point of the excretory system. In urodeles,
including the axolotl Ambystoma mexicanum, as well as some primitive
teleosts, PND morphogenesis appears to occur entirely by active cell migration
accompanied by cell rearrangements (Ballard
and Ginsburg, 1980; Poole and
Steinberg, 1981
; Poole,
1988
; Drawbridge et al.,
2003
). Therefore, the events of axolotl PND morphogenesis provide
an excellent system for studying directed cell migration in vivo.
During their migration, PND cells come into direct contact with somitic
mesoderm, lateral flank mesoderm and overlying epidermis, all of which are
potential sources of local guidance information. By transplantation and
rotation of epidermal grafts, Drawbridge et al.
(Drawbridge et al., 1995) have
shown that overlying epidermis provides directional cues to the migrating PND.
The PND `reads' this information along the anterior-posterior (AP) axis to
direct migration from anterior to posterior (A
P) and along the
dorsal-ventral (DV) axis to constrain migration to the PND pathway. This
overlying epidermis has been shown to secrete an extracellular matrix (ECM)
onto the migrating PND cells and their migration pathway
(Poole and Steinberg, 1981
;
Gillespie and Armstrong,
1986
). Because of evidence in other systems showing that ECM
components can provide not only a permissive substratum for cell migration but
also a source of directional cues (reviewed in
Boucaut et al., 1991
;
Winklbauer and Nagel, 1991
;
Johnson et al., 1992
;
Erickson and Perris, 1993
;
Perris, 1997
;
Perris and Perissinotto,
2000
), we hypothesized that components of the epidermally secreted
ECM might provide the PND with a migration substratum, directional information
or both. Using a method described by Löfberg et al.
(Löfberg et al., 1985
) of
"in vivo adsorption of embryonic extracellular matrix onto a
`microcarrier' of Nuclepore filter", we have examined the potential role
of epidermally derived ECM in axolotl PND migration. The results presented
here provide evidence that this ECM is a source of directional guidance cues
for PND cells.
We also wanted to identify specific ECM components that might serve as
directional cues, as well as the corresponding receptors used by PND cells to
recognize and respond to information from the ECM. Lallier et al.
(Lallier et al., 1996) have
reported that the expression pattern of the
6 integrin subunit during
Xenopus development includes the elongating PND. Therefore, we have
set out to determine whether axolotl embryos exhibit a similar
6
integrin expression pattern and, if so, whether
6 integrins play any
role in PND extension. The anti-
6 integrin monoclonal antibody GoH3
blocks binding of
6-containing integrins to laminin proteins
(Sonnenberg et al., 1986
;
Knapp et al., 1989
;
Aumailley et al., 1990
). Using
in vivo application of this and other function-blocking antibodies, we provide
direct evidence that
6 and ß1 integrins, and laminin 1 are
required components of the PND migration system.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
ECM-bearing microcarriers: orientation and transplantation
Polycarbonate membranes (Poretics) of pore size 0.4 µm were cut with
iris scissors into approximately 0.5 mm squares. Using sharpened tungsten
needles, epidermal flaps of approximately four somite widths were made on one
side of stage 22 donor embryos. Membrane fragments (`carriers') were then
placed beneath the epidermal flaps and held there with glass bridges. Embryos
were allowed to continue development overnight (to approximately stage 30) at
room temperature, during which time ECM was deposited onto the carriers. The
side of the carrier apposed to the epidermis is termed the `E' face; the side
apposed to the mesoderm is termed the `M' face.
For transplantation of ECM-bearing carriers, epidermal flaps were cut over the PND pathway of stage 22 hosts. ECM-conditioned carriers were removed from donor embryos and placed under the host epidermal flap, presenting either the `E' or the `M' face of the ECM-bearing carrier to the migrating PND primordium. The flap was then closed and allowed to heal. Various rotations of the ECM-conditioned carriers (90° dorsal, 90° ventral, 180° or no rotation) were made prior to their introduction into hosts.
To present epidermally deposited ECM to the underlying mesoderm, a carrier
must be turned over before re-implantation. This reverses either its AP or its
DV axis. This axial reversal can be undone (`unrotated' carrier) by collecting
ECM on one side of the embryo and presenting it to the mesoderm on the
opposite side. For unrotated and 90° rotated `E' carriers, ECM was
collected on the left-hand side of donor embryos then transplanted to the
right-hand side of hosts. Thus, both the AP and DV orientation of unrotated
carriers relative to host embryos were maintained. `90° dorsal' and
`90° ventral' rotations realign both the AP and DV axes of the
transplanted ECM. `90° dorsal' rotation aligns the ECM's original AP
axis with the host's V
D axis and its original D
V axis with the
host's A
P axis. `90° ventral' rotation aligns the ECM's original
A
P axis with the host's D
V axis and its original D
V axis with
the host's P
A axis.
In the case of 180° rotations of `E' carriers, ECM was collected on the left-hand side of donor embryos and then transplanted to the left-hand side of hosts to reverse only the AP axis of the transplanted ECM relative to that of the host PND pathway.
ECM for unrotated or 180° rotated `M' carriers was collected on the left-hand side of donor embryos and transplanted to the left-hand side of hosts. Thus, unrotated `M' ECM matched both the AP and DV axes of the underlying host PND pathway. `M' carriers rotated 180° reversed both AP and DV axes of the transplanted ECM relative to host tissues.
Host embryos were cultured to stage 28 at room temperature and fixed in
modified Karnovsky's fixative (1.5% paraformaldehyde, 1.5% glutaraldehyde and
0.1 M phosphate buffer, pH 7.4). Overlying epidermis was then peeled away and
the carrier dissolved in chloroform. PND morphology was then observed and
photographed. In all cases, the unoperated side of each host embryo was
examined as an internal control for normal PND migration. Embryos in which PND
migration was inhibited on the unoperated side were discarded, because they
probably underwent abnormal development unrelated to our experimental
manipulations. Fisher's exact test and likelihood ratio 2
statistical analysis were performed on this data.
Antibody treatment of embryos
Embryos were reared to stage 20-21 prior to injections. The Picospritzer II
(General Valve) was used to inject bovine serum albumin (BSA), antibodies and
Fab fragments under conditions previously described
(Thibaudeau et al., 1993).
Antibodies were obtained from the following sources: purified monoclonal
anti-human
6 integrin (GoH3) (Pharmingen); monoclonal,
function-blocking anti-ß1 chicken integrin, (Sigma); monoclonal, non
function-blocking anti-human ß1 integrin (Chemicon International); and
polyclonal, anti-mouse laminin-1/E8 fragment (gift of P. Yurchenco, UMDNJ). A
polyclonal anti-laminin antibody against the basement membrane of an EHS mouse
sarcoma (Sigma) was also used in whole mount immunocytochemistry (ICC).
Embryos stained for laminin proteins were sectioned using standard techniques.
All antibodies used in these experiments were characterized by western
analysis and immunoprecipitation (IP) to insure antigen specificity. Fab
fragments were made using papain digestion according to the manufacturer's
recommended conditions (Pierce).
Subepidermal injections of all agents to be tested were typically made
along the lateral aspect of the embryo, just below the developing somites at
points dorsal to the PND tip, immediately caudal to the tip and also along the
migratory pathway, at 1 mg ml1 concentrations. Successful
injections resulted in raised `blisters' at the injection site that flattened
upon dispersal of the sample. After injections, embryos were transferred to
fresh agarose-coated dishes containing HBSt with antibiotics and allowed to
continue development overnight at room temperature, followed by fixation and
manual removal of the overlying epidermis. For each set of injections, the
location of the PND tip was determined for both the injected and uninjected
sides, since diffusion of injected proteins across the embryonic midline does
occur (Zackson and Steinberg, 1989;
Thibaudeau et al., 1993).
Whole mount immunocytochemistry
Albino axolotl embryos were treated according to the methods described by
Smith and Armstrong (Smith and Armstrong,
1990). Embryos were first fixed overnight at room temperature, in
Dent's fixative (80% methanol, 20% dimethylsulfoxide, v/v) and then stored in
absolute methanol at 20°C until use. Samples were rehydrated in TBS
(0.05 M Tris-HCl, 0.85% NaCl, pH 7.6) then incubated in the appropriate
primary antibody, diluted in TBS with 0.2% BSA as follows:
6, 1:1000;
ß1 (blocking and non-blocking), 1:500; laminin, 1:50; laminin 1/E8,
1:100. Embryos were washed in at least five changes of TBS/0.1% Tween over 24
hours. Whole mounts were then incubated in a biotinylated goat anti-mouse,
goat anti-rat or goat anti-rabbit secondary antibody in TBS/0.2% BSA (1:1000
dilution), rinsed as before, then incubated in 1:1000
streptavidin/ß-galactosidase in TBS/0.1% Tween. Antibody binding was
detected by developing whole mounts in 0.42 mg ml1 X-gal in
10 mM sodium phosphate, pH 7.2, 150 mM NaCl, 3.0 mM potassium ferricyanide,
3.0 mM potassium ferrocyanide, 1.0 mM MgCl2. For staining with
6 and ß1 antibodies, epidermis was peeled from fixed embryos prior
to initial rehydration. For laminin and LM-1, E8 fragment antibody staining,
the epidermis was kept intact and the embryos were permeabilized with Dent's
fixative prior to antibody introduction. Transverse sections of
LM-stained were made using standard histological techniques.
Assessment of the extent of PND migration
In the axolotl, PND migration occurs in synchrony with the wave of somite
segmentation (Gillespie et al.,
1985; Gillespie and Armstrong,
1986
). Gillespie and Armstrong
(Gillespie and Armstrong,
1986
) showed that the posterior tip of the axolotl PND is located
approximately 2 somite widths anterior to the most posterior somite fissure
throughout the entire period of PND migration. Thus, segmenting somites serve
as anatomical landmarks to which the extent of PND migration can be compared.
In agreement with Gillespie and Armstrong, we found that the posterior tips of
PNDs in control embryos are found one, two and sometimes three somite widths
anterior to the most posterior somite fissure; these were scored as `last
somite minus 1' (LS MINUS 1), LS MINUS 2 and LS MINUS 3, respectively. Thus,
scores `anterior to LS MINUS 3' indicate inhibition of PND migration. One-way
ANOVA statistical analysis was also performed on this data.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To assay the ability of epidermally derived ECM to direct PND migration,
the `E' face of such conditioned polycarbonate carriers was presented to the
PND and PND pathway of stage 22 host embryos in the following orientations:
(1) unrotated, preserving both AP and DV axes; (2) rotated by 180°,
reversing the AP axis while maintaining the DV axis; (3) rotated 90°
dorsally; or (4) rotated 90° ventrally
(Fig. 1). In the last two
cases, the carrier's original AP orientation was aligned V
D or
D
V with the host, its original DV axis also being rotated
correspondingly. The results of these experiments were compared with those
obtained with unconditioned, control carriers. In addition, mesodermally
derived ECM (i.e. the `M' face of conditioned carriers) was also presented to
the migrating PND. The results are summarized in
Table 1.
|
|
|
Host PNDs were also presented with the side of the microcarrier that had been apposed to the mesoderm of the ECM donor (the `M' side). Experiments in which the AP and DV axes of the implanted `M' carrier were the same as those of the host embryo resulted in normal PND migration. When the AP axis of the `M' carriers was rotated 180° relative to that of the host, PND migration was unaffected by this reorientation and these carriers also supported normal migration.
Inhibition of laminin binding to `E' carriers prevents redirection of
PND migration
Exposure of `E' carriers to a polyclonal, anti-laminin antibody revealed
the presence of laminin proteins on the carriers (data not shown). This raises
the possibility that laminins might be involved in permitting and/or guiding
PND migration. There is substantial evidence in other systems that
extracellular components, particularly laminins, provide both a permissive
substratum and also directional cues for cell migration
(Lallier et al., 1992;
Bronner-Fraser, 1993
;
Perris et al., 1996
;
Garcia-Castro et al., 1997
;
Luckenbill-Edds, 1997
).
To determine whether laminin 1, in particular, provides the migrating axolotl PND with a migration substratum, directional information or both, host embryos were presented with ECM-conditioned `E' carriers that had been treated prior to transplantation with the function-blocking antibody against the laminin-1/E8 cell-binding domain (1 mg ml1). These antibody-treated carriers were rotated 90° ventrally before introduction into host embryos. In most cases, the PND stopped migrating under the carriers, as was seen when unconditioned carriers were presented to host PNDs (Table 1). In no case was the host PND deflected ventrally. By contrast, 90° ventral rotations of `E' carriers that had not been treated with the anti-laminin-1/E8 antibody often caused ventral deflection. Thus, blocking the E8 cell-binding domain of laminin 1 in the epidermally derived ECM bound to rotated carriers prevents their re-orientation of PND migration.
Laminin 1 and its receptor (6ß1 integrin) are expressed
during PND migration
Whole mount ICC with either a polyclonal `anti-laminin' antibody or an
anti-laminin-1/E8 domain-specific antibody revealed the presence of laminin in
the head and lateral flank of stage 24-28 embryos. Analysis of transverse
sections of these embryos reveals that laminin 1 is present at the base of
ectodermal epithelial cells, within the basal lamina overlying the head and
along the lateral flank as well (Fig.
3C).
|
Antibodies that block 6 and ß1 integrin function disrupt
PND migration
Function-blocking antibodies against the 6 and ß1 integrin
subunits were used to determine whether blocking active sites on the
6ß1 integrin receptor inhibits PND migration. Subepidermal
injection of 1 mg ml1 anti-
6 integrin GoH3 Fab
fragments significantly inhibited PND migration, such that the PND tip was
located anterior to LS MINUS 3 in more than half the cases observed
(P=0.005). In BSA-injected sibling controls, most cases showed the
normal PND migration at LS MINUS 1 to LS MINUS 3
(Fig. 4A,B;
Fig. 5A). Sub-epidermal
injection of anti-ß1 integrin Fabs resulted in inhibition of PND
migration similar to that observed with the
6-blocking antibody
(Fig. 5C; P=0.046).
|
|
Antibody blocking the laminin-1/E8 domain inhibits PND migration
If the preceding results reflect more efficient blocking of the
6ß1 integrin when antibodies to both subunits are injected
together, blocking this integrin's ligand (the E8 domain of laminin 1) should
be equivalent to blocking both
6 and ß1 together. This would also
provide a direct test of the involvement of laminin 1 in PND migration.
Injection of anti-laminin-1/E8 Fab fragments caused pronounced inhibition
of PND migration. In these experiments, the tip of the duct was typically
found anterior to LS MINUS 3 (Fig.
5D; P<0.0001). In sibling control embryos injected
with BSA, this level of inhibition was never observed. These results are
comparable to those observed with the combination of 6 and ß1
antibody injections (Fig. 4C,
Fig. 5D). We therefore conclude
that inhibition of PND migration when antibodies to both
6 and ß1
are co-injected reflects the specific blocking of
6ß1
integrin.
In addition to antibodies, laminin-1/E8 peptide fragments were also
injected into embryos. Such injections also caused inhibition of PND
migration, presumably because of competition with endogenous laminin for
binding to 6ß1 integrin (Fig.
5E; P=0.008).
Injection of control proteins and antibodies does not inhibit PND
migration
To examine the possibility that our Fab fragment injection results were due
to non-specific effects of the injected proteins, control injections were also
performed. Injection of a nonfunction-blocking anti-ß1 antibody into
embryos had little effect on PND migration, demonstrating that injected
antibodies must bind to a functional epitope in order to inhibit PND migration
in our assays (Fig. 5F;
P=0.058). Likewise, when a 1:2 molar ratio of anti-laminin-1/E8
antibody:E8 fragments was injected, PND migration was essentially normal
(Fig. 5G; P=0.0006),
suggesting that the ability of the anti-E8 antibody to perturb PND migration
depends on its E8-binding activity. These controls demonstrate that the
observed inhibition of PND migration by microinjection of function-blocking
antibodies and Fab fragments is due to the inhibition of specific molecular
domains necessary for PND migration.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Our carrier implantation experiments also allowed us to determine whether ECM deposited on polycarbonate carriers by lateral mesoderm (`M' ECM) underlying the PND can influence PND migration. The data in Table 1 reveal that both mesodermal ECM and unrotated epidermal ECM are much more effective than polycarbonate carriers alone at supporting PND migration. Thus, both epidermal and mesodermal ECM provide a permissive substratum for PND migration. However, `M' ECM supports PND migration equally well when aligned with or opposed to the AP and DV axes of host ECM, whereas `E' ECM only supports normal PND migration when its AP and DV axes are aligned with those of the host. Thus, we conclude that `M' ECM permits, but does not guide PND, migration, whereas `E' ECM both permits and guides it.
Although changes in the direction of PND migration with carrier rotations
were observed in significant numbers of cases, both normal and arrested PND
migration were also frequently observed. These results might be explained by
the fact that removal of epidermis does not completely remove already-secreted
epidermal ECM from the PND surface (J.D., unpublished). In our ECM-conditioned
carrier transplantation experiments, ECM is likely to be left on the PND
following epidermal removal, leaving some host-derived AP guidance
information available to the PND. We speculate that this information competes
with information from the transplanted, donor ECM bound to the carrier,
presenting the migrating PND with conflicting directions when the carrier is
rotated. The PND responds to such conflicting information by ceasing migration
altogether or by following the more abundant of the two competing sets of
guidance cues.
Role of 6ß1 integrins and laminin 1 in PND migration
Can the PND-guiding property of `E' ECM be traced to specific cell
receptors and ECM components? Our results demonstrate the presence of both
6 and ß1 integrin subunits on the PND itself and of laminin 1 on
the flank that serves as the PND pathway. We also show that blocking either
laminin 1's integrin-binding sites or the
6ß1 integrin receptor
that binds to them inhibits PND migration. Moreover, a function-blocking
anti-laminin-1 antibody neutralizes the ability of ECM bound to a rotated
carrier implant to redirect PND migration. Thus, laminin 1 is a required
component of the PND migratory pathway and
6ß1 integrins are a
required component of the PND pathfinding apparatus.
Laminin proteins have been reported to provide both permissive and
directive substrata for migrating cells
(Lallier and Bronner-Fraser,
1991; Yao et al.,
1996
; Bendel-Stenzel et al.,
1998
; Jones et al.,
2000
). Furthermore, laminins have also been shown to be required
components of the PND (Wolffian duct) migration substratum in both chick and
mouse embryos (Bellairs et al.,
1995
; Willem et al.,
2002
). Two possibilities present themselves here based upon our
findings either laminin 1 itself provides both permissive and
directive PND guidance information or laminin 1 provides only a permissive
substratum, directional cues being provided by a different component of the
ECM.
Of the ducts confronted with `E' carriers rotated by 90°, 32% were deflected in the corresponding direction and another 32% were blocked beneath the carrier. By contrast, of the ducts confronted with anti-laminin-1-treated `E' carriers rotated by 90°, 0% were deflected in the corresponding direction, whereas 64% were blocked beneath the carrier. These data suggest that application of anti-laminin-1 to `E' carriers prevents the ECM-mediated duct diversion by blocking the further migration of those ducts that would otherwise have been diverted. Those ducts consequently end up in the `stops under carrier' category. There is no significant effect of antibody treatment of the carriers on the fraction of ducts that migrate normally. These are the results to be expected if, in the absence of antibody, a proportion of the ducts beneath the rotated carrier adhere primarily to residual host ECM and are thus unaffected by the ECM on the carrier, whereas the remaining ducts adhere primarily to the laminin 1 on the carrier and are diverted. Thus, anti-laminin-1 treatment of the ECM-bearing carrier would only prevent ducts adhering primarily to the carrier's ECM from migrating further.
Possible models for axolotl PND guidance
Although the studies reported here indicate that an interaction between
6ß1 integrins on PND cells and laminin 1 on their migration
substratum is required for PND migration, they do not tell us whether laminin
1 provides permissive cues, directional cues or both to the migrating PND.
Recently, Drawbridge et al. (Drawbridge et
al., 2000
) identified the ligand-binding component of the Ret
receptor, glial-cell-line-derived neurotrophic family receptor
-1
(GFRa-1), and its ligand, glial-cell-line-derived neurotrophic factor (GDNF),
as components of the PND directional pathfinding machinery. They proposed a
model in which PND cells expressing GFRa-1 migrate up a gradient of GDNF to
the cloaca. However, GDNF is secreted not by epidermal cells but by cells of
the lateral mesoderm (Moore et al.,
1996
; Sanchez et al.,
1996
; Homma et al.,
2000
). Thus, the data presented here and that of Drawbridge et al.
(Drawbridge et al., 2000
)
suggest at least two possible models for PND guidance.
First, it is known that growth factors can be deposited in ECM from which
they can subsequently be released (Taipale
and Keski-Oja, 1997). Therefore, our present results and those of
Drawbridge et al. (Drawbridge et al.,
2000
), support a model of normal PND guidance in which the lateral
flank epidermis secretes a laminin-1-containing ECM overlying the migrating
PND. In this model, lateral mesoderm posterior to the migrating duct secretes
GDNF, which binds to epidermal ECM in an A
P gradient. The PND cells
migrate by attachment to the laminin-1/E8 cell-binding domain via their
6ß1 integrins and chose their direction by migrating up the
gradient of ECM-bound GDNF.
Alternatively, epidermally deposited laminin 1 and mesodermally provided
GDNF might provide the migrating PND with overlapping but independent sets of
guidance cues. Direct evidence from this study and that of Drawbridge et al.
(Drawbridge et al., 1995)
shows that laminin-1-containing epidermal ECM provides directional information
to the migrating duct. However, Drawbridge et al.
(Drawbridge et al., 1995
) also
showed that epidermal guidance cues are present throughout the tailbud stages
of development and are therefore not responsible for the observed temporal
restriction on PND migration (Poole and
Steinberg, 1982
; Gillespie and
Armstrong, 1986
). They proposed that two sets of guidance cues
govern the timing and direction of PND migration: cues from the epidermis are
required for directional information; and cues derived from lateral mesoderm
are required to restrict migration temporally
(Drawbridge et al., 1995
;
Drawbridge et al., 2003
;
Drawbridge and Steinberg,
1996
). Therefore, a second model of PND guidance is also possible,
in which laminin-requiring epidermal cues and mesodermally derived GDNF
provide overlapping but independent sets of guidance information.
In summary, the present study identifies the
laminin-1/6ß1-integrin ligand/receptor system as essential for PND
guidance in axolotl embryos. Furthermore, these data, integrated with previous
studies, suggest two possible ways in which PND guidance might be accomplished
in these embryos. These two alternative models suggest direct tests that will
help future workers to elucidate the molecular and cellular basis of this
guidance system in further detail.
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
Footnotes |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aumailley, M. and Gayraud, B. (1998). Structure and biological activity of the extracellular matrix. J. Mol. Med. 76,253 -265.[CrossRef][Medline]
Aumailley, M., Timpl, R. and Sonnenberg, A.
(1990). Antibody to integrin 6 subunit specifically
inhibits cell-binding to laminin fragment 8. Exp. Cell
Res. 188,55
-60.[Medline]
Ballard, W. W. and Ginsburg, A. S. (1980). Morphogenetic movements in acipenserid embryos. J. Exp. Zool. 213,69 -103.
Bellairs, R., Lear, P., Yamada, K. M., Rutishauser, U. and Lash, J. W. (1995). Posterior extension of the chick nephric (Wolffian) duct: the role of fibronectin and NCAM polysialic acid. Dev Dyn. 202,333 -342.[Medline]
Bendel-Stenzel, M., Anderson, R., Heasman, J. and Wylie, C. (1998). The origin and migration of primordial germ cells in the mouse. Semin. Cell Dev. Biol. 9, 393-400.[CrossRef][Medline]
Bordzilovskaya, N. P., Dettlaff, T. A., Duhon, S. T. and Malacinski, G. M. (1989). Developmental-stage series of axolotl embryos. In The Developmental Biology of the Axolotl (eds J. B. Armstrong and G. M. Malacinski), pp.201 -209. New York: Oxford University Press.
Boucaut, J. C., Darribère, T., Shi, D. L., Riou, J. F., Delarue, M. and Johnson, K. E. (1991). The amphibian embryo: An experimental model for the in vivo analysis of interactions between embryonic cells and extracellular matrix molecules. In vivo 5,473 -481.[Medline]
Bronner-Fraser, M. (1993). Environmental influences on neural crest cell migration. J. Neurobiol. 24,233 -247.[Medline]
Davies, J. (2001). Intracellular and extracellular regulation of ureteric bud morphogenesis. J. Anat. 198,257 -264.[CrossRef][Medline]
Drawbridge, J. and Steinberg, M. S. (1996). Morphogenesis of the axolotl pronephric duct: a model system for the study of cell migration in vivo. Int. J. Dev. Biol. 40,709 -713.[Medline]
Drawbridge, J., Wolfe, A., Delgado, Y. and Steinberg, M. S. (1995). The epidermis is a source of directional information for the migrating pronephric duct in Ambystoma mexicanum embryos. Dev. Biol. 172,440 -451.[CrossRef][Medline]
Drawbridge, J., Meighan, C. M. and Mitchell, E. A. (2000). GDNF and GFRa-1 are components of the axolotl pronephric duct guidance system. Dev. Biol. 228,116 -124.[CrossRef][Medline]
Drawbridge, J., Meighan, C. M., Lumpkins, R. and Kite, M. (2003). Pronephric duct extension in amphibian embryos: migration and other mechanisms. Dev Dyn. 226, 1-11.[CrossRef][Medline]
Erickson, C. A. and Perris, R. (1993). The role of cell-cell and cell-matrix interactions in neural crest morphogenesis. Dev. Biol. 159,60 -74.[CrossRef][Medline]
Garcia-Castro, M., Anderson, R., Heasman, J. and Wylie, C.
(1997). Interactions between germ cells and extracellular matrix
glycoproteins during migration and gonad assembly in the mouse embryo.
J. Cell Biol. 138,471
-480.
Gillespie, L. L. and Armstrong, J. B. (1986). Morphogenetic waves in the development of the lateral mesoderm in the Mexican axolotl (Ambystoma mexicanum) and their relationship to pronephric duct migration. J. Exp. Zool. 237,327 -338.
Gillespie, L. L., Armstrong, J. B. and Steinberg, M. S. (1985). Experimental evidence for a proteinaceous presegmental wave required for morphogenesis of axolotl mesoderm. Dev. Biol. 107,220 -226.[Medline]
Homma, S., Oppenheim, R. W., Yaginuma, H. and Kimura, S.
(2000). Expression pattern of GDNF, c-ret and GFRs
suggests novel roles for GDNF ligands during early organogenesis in the chick
embryo. Dev. Biol. 217,121
-137.[CrossRef][Medline]
Johnson, K. E., Darribère, T. and Boucaut, J. C. (1992). Ambystoma maculatum gastrulae have an oriented fibronectin-containing extracellular matrix. J. Exp. Zool. 261,458 -471.[Medline]
Jones, C. R., Dehart, G., Gonzales, M. and Goldfinger, L. (2000). Laminins: an overview. Microsc. Res. Tech. 51,211 -213.[CrossRef][Medline]
Knapp, W., Dorken, B. and Rieber, E. P., eds (1989). Leucocyte typing IV: White Cell Differentiation Antigens. New York: Oxford University Press.
Kramer, R., Vu, M., Cheng, P., Ramos, D., Timpl, R. and Waleh, N. (1991). Laminin-binding integrin alpha 7 beta 1: functional characterization and expression in normal and malignant melanocytes. Cell Regul. 2, 805-317.[Medline]
Lallier, T. and Bronner-Fraser, M. (1991). Avian neural crest cell attachment to laminin: involvement of divalent cation dependent and independent integrins. Development 113,1069 -1084.[Abstract]
Lallier, T., LeBlanc, G., Artinger, K. B. and Bronner-Fraser,
M. (1992). Cranial and trunk neural crest cells use different
mechanisms for attachment to extracellular matrices.
Development 116,531
-541.
Lallier, T., Whittaker, C. and DeSimone, D.
(1996). Integrin 6 expression is required in nervous
system development in Xenopus laevis. Development
122,2539
-2554.
Löfberg, J., Nynäs-McCoy, A., Olsson, C., Jönsson, L. and Perris, R. (1985). Stimulation of initial neural crest cell migration in the axolotl embryo by tissue grafts and extracellular matrix transplanted on microcarriers. Dev. Biol. 107,442 -459.[Medline]
Luckenbill-Edds, L. (1997). Laminin and the mechanism of neuronal outgrowth. Brain Res. Rev. 23, 1-27.[CrossRef][Medline]
Moore, M. W., Klein, R. D., Farinas, I., Sauer, H., Armanini, M., Phillips, H., Reichardt, L., Ryan, A., Carver-Moore, K. and Rosenthal, A. (1996). Renal and neuronal abnormalities in mice lacking GDNF. Nature 382, 76-79.[CrossRef][Medline]
Perris, R. (1997). The extracellular matrix in neural crest-cell migration. Trends Neurosci. 20, 23-31.[CrossRef][Medline]
Perris, R. and Perissinotto, D. (2000). Role of the extracellular matrix during neural crest cell migration. Mech. Dev. 95,3 -21.[CrossRef][Medline]
Perris, R., Brandenberger, R. and Chiquet, M. (1996). Differential neural crest cell attachment and migration on laminin isoforms. Int. J. Dev. Neurosci. 14,297 -314.[CrossRef][Medline]
Poole, T. J. (1988). Cell rearrangement and directional migration in pronephric duct development. Scan. Microsc. 2,411 -415.
Poole, T. J. and Steinberg, M. S. (1981). Amphibian pronephric duct morphogenesis: segregation, cell rearrangement and directed migration of the Ambystoma duct rudiment. J. Embryol. Exp. Morph. 63,1 -16.[Medline]
Poole, T. J. and Steinberg, M. S. (1982). Evidence for the guidance of pronephric duct migration by a craniocaudally traveling adhesion gradient. Dev. Biol. 92,144 -158.[Medline]
Sanchez, M. P., Silos-Santiago, I., Frisen, J., He, B., Lira, S. A. and Barbacid, M. (1996). Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382,70 -73.[CrossRef][Medline]
Saxén, L. (1987). Organogenesis of the Kidney. Cambridge University Press.
Saxén, L., Sariola, H. and Lehtonen, E. (1986). Sequential cell and tissue interactions governing organogenesis of the kidney. Anat. Embryol. 175, 1-6.[Medline]
Smith, S. C. and Armstrong, J. B. (1990). Heart induction in wild-type and cardiac mutant axolotls (Ambystoma mexicanum). J. Exp. Zool. 254, 48-54.[Medline]
Sonnenberg, A., Daams, H. and van der Valk, M. A. (1986). Development of mouse mammary gland: Identification of stages in differentiation of luminal and myoepithelial cells using monoclonal antibodies and polyvalent antiserum against keratin. J. Histochem. Cytochem. 34,1037 -1046.[Abstract]
Taipale, J. and Keski-Oja, J. (1997). Growth
factors in the extracellular matrix. FASEB J.
11, 51-59.
Thibaudeau, G., Drawbridge, J., Dollarhide, A. W., Haque, T. and Steinberg, M. S. (1993). Three populations of migrating amphibian embryonic cells utilize different guidance cues. Dev. Biol. 159,657 -668.[CrossRef][Medline]
Willem, M., Miosge, N., Halfter, W., Smyth, N., Jannetti, I.,
Burghart, E., Timpl, R. and Mayer, U. (2002). Specific
ablation of the nidogen-binding site in the laminin 1 chain interferes
with kidney and lung development. Development
129,2711
-2722.
Winklbauer, R. and Nagel, M. (1991). Directional mesoderm cell migration in the Xenopus gastrula. Dev. Biol. 148,573 -589.[Medline]
Yao, C., Ziober, A., Sutherland, A., Mendrick, D. and Kramer,
R. (1996). Laminins promote the locomotion of skeletal
myoblasts via the 7 integrin receptor. J. Cell
Sci. 109,3139
-3150.
Zackson, S. L. and Steinberg, M. S. (1986). Cranial neural crest cells exhibit directed migration on the pronephric duct pathway: further evidence for an in vivo adhesion gradient. Dev. Biol. 117,342 -353.[Medline]