PERSPECTIVES
familiar Reductionist approach has never
worked very well for patterned ground.
The second obstacle is related to the first
one but is purely technical: How can the
3D effects of repeated freeze-thaw cycles
on a given volume of rocky soil be simulated over hundreds of years? Kessler and
Werner solve the conceptual problem by
applying a self-organization approach (14)
that takes into account spatial and temporal scales greater than those of the individual stones and sand grains. They couple
this approach with computer simulations
that track the movements of thousands of
individual stones within a field of cyberspace tundra (1).
Kessler and Werner’s simple model
answers a question as basic as “Why is the
sky blue?” and makes sense with what is
seen on the ground in polar or alpine environments. The work is also exciting
because it embodies a new point of view
that is affecting the entire field of geomorphology (the subdiscipline of geology that
others have enviously described as the “science of scenery”). The field is experiencing a paradigm shift from a reductionist
approach toward concepts such as universality and self-organization (15).
Reductionism assumes that all characteristics of geomorphic features, from ripples to sand seas, can ultimately be predicted from first principles applied to fundamental particles. The geomorphic phenomena on Earth’s surface are then the mere byproducts of much smaller scale processes.
Self-organization offers a different viewpoint (16). Landforms are products of selfassembling hierarchies of processes.
Interacting groups of mechanisms, like the
three discussed above for patterned ground,
are linked by feedbacks that span a range of
spatial and temporal scales. In Kessler and
Werner’s model, the positions and contours
of the separate domains of fine and coarse
particles—which have developed over
decades to centuries and have length scales
on the order of meters—influence the freezing and thawing of ice lenses located within each square centimeter of the soil
domain. These lenses freeze and thaw over
hourly to monthly time scales, and it is their
orientation and amount of heave that maintain the overall landform.
Hence, smaller, faster processes are
slaved by larger, slower ones within the patterned ground system. Such interactions
can have unexpected results, and selforganizing systems typically have emergent
properties that are not predictable from the
physics of their fundamental particles.
There is nothing in the physics of a shovelful of stony mud that can predict the emergence of an intricate pattern of interlaced,
stone-bordered polygons covering many
square meters. According to the self-organization paradigm, many geomorphic phenomena on Earth’s surface are responsible
for their own development and maintenance. A landform is not just a by-product
of processes operating at the scale of its
fundamental particles; it can only be understood at its own greater-than-sand scales.
There are many more types of patterned
ground than those investigated by Kessler
and Werner, and no single model can explain
them all. But their approach gives us a new
investigative tool to try out on other patterned features. Of course, models must be
treated with caution, because they can mimic
the work of nature but use the wrong mechanisms. Also, similar types of patterned
ground can arise in different settings as a
result of quite different mechanisms. Some
types of patterned ground have very simple
forms, and the simpler the form, the easier it
is for different processes to create them.
The self-organization perspective of
Kessler and Werner (1) paper brings up
some interesting questions. If self-organized
entities are widespread in Earth’s most desolate environments, are the milder climes
teeming with them unnoticed? Is self-organization as inevitable as gravity? Self-organization entails self-making and self-maintaining, and these are characteristics of living things. So where is the division? And do
self-organized entities compete with each
other for growing space and for the energy
flows that sustain them? For instance, do
sorted circles and polygons somehow fight
it out for possession?
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
M. A. Kessler, B. T. Werner, Science 299, 380 (2003).
B. T. Werner, T. M. Fink, Science 260, 968. (1993).
B. T. Werner, B. Hallet, Nature 361, 142 (1993).
B. T. Werner, Geology 23, 1107 (1995).
L. J. Plug, B. T. Werner, Nature 417, 929 (2002).
A. L. Washburn, Geol. Soc. Am. Bull. 67, 823 (1956).
———, Geocryology (Wiley, New York, 1980).
———, Plugs and Plug Circles: A Basic Form of
Patterned Ground, Cornwallis Island, Canada—Origin
and Implications (Geological Society of America,
Boulder, CO, 1997).
O. Nordenskjöld, Die Polarwelt (Tuebner, Leipzig,
1909).
F. Nansen, Spitzbergen (Brockhaus, Leipzig, 1922).
S. Taber, J. Geol. 37, 428 (1929).
B. Hallet, S. Prestrud, Quat. Res. 26, 81 (1986).
S. P. Anderson, Geol. Soc. Am. Bull. 100, 609 (1988).
G. Nicolis, I. Prigogine, Self-Organization in Nonequilibrium Systems (Wiley, New York, 1977).
P. R. Wilcock, R. M. Iverson, Eds., Prediction in
Geomorphology, vol. 135 of Geophysical Monograph
Series (American Geophysical Union, Washington,
DC, 2002).
B. Hallet, Can. J. Phys. 68, 842 (1990).
J. Büdel, Klima-Geomorphologie (Borntraeger, Berlin,
1977).
DEVELOPMENT
What Makes an Embryo Stick?
Asgerally T. Fazleabas and J. Julie Kim
ow does an embryo know where
and when to become attached to the
lining of the uterus, which is
accommodating for only a narrow window of time? Implantation of the embryo
is a complex biological process that is
species specific. In humans, successful
implantation requires an orchestrated
synchrony between an appropriately developed embryo and the hormonally primed
receptive endometrium. In clinical medicine, the past two decades have seen a rev-
:
H
The authors are in the Department of Obstetrics and
Gynecology, University of Illinois, Chicago, IL 60612,
USA. E-mail: asgi@uic.edu
olution in the treatment of infertility, yet
embryo implantation still remains a major
limiting factor in assisted reproductive
therapies. Despite significant progress in
reproductive research (1), many fundamental questions about implantation remain to
be resolved. On page 405 of this issue,
Genbacev et al. (2) cleverly apply lessons
learned from vascular biology to elucidate
the molecules involved in the initial step of
implantation. They demonstrate that Lselectin—a molecule that enables circulating leukocytes to bind to the blood vessel
endothelium [reviewed in (3)]—is commandeered by the human blastocyst to initiate interactions with the uterine lining.
www.sciencemag.org
SCIENCE
VOL 299
Studying biopsies of human endometrial tissue, Genbacev et al. describe the
up-regulation of carbohydrates on the
surface of the receptive uterus that bind
to L-selectin. Coincident with this, the
trophoblast cells of the implantation-competent human embryo (blastocyst) begin to
express L-selectin after release of the blastocyst from its zona pellucida coat. The
authors next investigated the physiological
importance of the interaction between Lselectin and its oligosaccharide ligands.
They coated polystyrene latex beads with
an oligosaccharide that binds to L-selectin
(6-sulfo sLex) and observed that the beads
bound avidly to trophoblast cells in the placental villous tissues under conditions of
shear stress that mimic those of the uterus.
(The shear stress exerted by blood flow is
known to be necessary for optimal Lselectin–mediated adhesion of leukocytes
to the vasculature.) In a reverse experiment,
17 JANUARY 2003
355
they found that isolated trophoblasts bound
preferentially to uterine epithelial cells
from endometrial tissue harvested during
the receptive, but not the nonreceptive, period. These findings suggest that the interaction between L-selectin expressed by trophoblast cells and its oligosaccharide ligands expressed by the hormonally primed
uterus may constitute the initial step in the
implantation process (see the figure).
In vascular biology, the primary goal of
selectins is to promote the rolling of leukocytes along the endothelium. Rolling is a
prerequisite for white blood cells to adhere
firmly to the endothelium, before they
Ovary
interactions of other cell adhesion molecules (integrins, trophinin, HB-EGF) with
their ligands may contribute to the stable
adhesion of the embryo to the uterine
endometrium, which takes place later during implantation (see the figure). Could
L-selectin signaling pathways influence
the expression of other cell adhesion molecules? Certain types of infertility are associated with the lack of expression of the
αvβ3 integrin by uterine epithelial cells (5).
A consequence of this might be the inability of the blastocyst to form an adhesion
complex after apposition with the uterine
surface, leading to implantation failure.
A
CL
B
C
Other adhesion
molecules,
i.e., integrins
Progesterone
and estrogen
D
L-selectin
L-selectin ligands
?
Signaling cascades
(MAPK?)
Homing mechanism
to maternal vasculature?
L-selectin, a bridge for implantation. (A) After ovulation, the corpus luteum (CL) of the ovary
secretes progesterone and estrogen, which prepare the uterine lining for embryo attachment and
implantation. One important modification is the up-regulation of oligosaccharide ligands (green) on
the epithelial cells of the uterine lining that bind to L-selectin (yellow). (B) Initial attachment of the
embryo to the endometrial lining depends on binding of L-selectin expressed by trophoblasts (dark
blue) of the blastocyst to oligosaccharide ligands expressed by the endometrium. (C) This, in turn, triggers signaling pathways that modify the uterine environment to permit more stable adhesion and successful invasion of the endometrium by trophoblasts. (D) Continued expression of L-selectin by trophoblasts could serve as a homing device, enabling them to connect with the maternal vasculature
(orange) and to establish the placenta.
move through the endothelial layer into the
tissues (3). Apposition of the embryo to the
uterine surface resembles the rolling behavior of leukocytes, because L-selectin is
involved and because initially the process is
relatively unstable. A fundamental question
yet to be answered concerns the molecular
trigger for the transition from the Lselectin–mediated loose adherence of the
embryo during the initial implantation step
to the tight adherence that enables the trophoblasts to transmigrate into the uterine
wall and establish the placenta. Does the
binding of L-selectin to its ligands activate
a signaling cascade similar to that activated
by leukocytes adhering to the endothelium
(4)? What are the downstream targets of
such a signaling cascade? The subsequent
356
A recent study (6) reported a significant
increase in pregnancy rates following
embryo coculture with endometrial cells in
women who had multiple pregnancy losses
after assisted reproduction. Intriguingly,
the pregnancy rates were also significantly
higher when the embryos were cocultured
with endometrial cells obtained at day 6
after ovulation. Genbacev and co-workers
discovered a marked increase in the expression of selectin-binding oligosaccharides
by the uterus at this time. Does coculture
enhance embryo-endometrial cross talk in
vitro, thus improving the ability of the blastocyst to adhere and implant successfully
after transfer to the uterus?
The intriguing observation of Genbacev
and colleagues that trophoblasts share
17 JANUARY 2003
VOL 299
SCIENCE
adhesion mechanisms with leukocytes
points to the unusual nature of trophoblast
cells. It is clear that the apposition of the
embryo during implantation shares many
features in common with leukocytes rolling
along the endothelium. The well-studied
mechanisms of adhesion in immune and
vascular biology could provide us with cellular clues delineating the intricacies of the
implantation process in humans. This transduction of knowledge from one area of
biology to another should provide valuable
insights for exploring comparable biological processes. Trophoblasts also share features characteristic of cancer cells. Both
cell types are invasive but cancer cell invasion is not controlled, whereas trophoblast
migration into the uterus is tightly regulated both temporally and spatially. Perhaps by
studying the trophoblast invasion process in
a physiological context, as Genbacev et al.
have done (2, 7), we can obtain new insights
into how proliferation of malignant cells
and their metastasis could be prevented.
Genbacev et al. identify one very specific adhesion interaction that may serve as
the first critical step in implantation. Their
observations raise fundamental biological
questions about the mechanism by which
an embryo attaches itself to the uterus.
How is L-selectin up-regulated after the
blastocyst “hatches” from the zona pellucida? Is this programmed induction associated with development of the embryo? Does
the increase in oligosaccharide ligands on
the surface of the receptive endometrium
enhance the expression of L-selectin on
trophoblast cells as a consequence of intimate maternal-embryo dialogue? After
apposition, which adhesion molecules trigger stabilization of the embryo? Which signaling pathways are set in motion that
modify the uterine environment to permit
successful invasion by trophoblasts? Is the
continued expression of L-selectin by
invading trophoblasts at the maternal-fetal
interface a homing device directing these
cells to the maternal vasculature?
Disruption of events very early in pregnancy may be responsible for nonchromosomal pregnancy loss, which continues to
be a significant clinical concern in human
reproduction. With the Genbacev et al.
study, we can now begin to unravel the
molecular mechanisms that are critical for
understanding the process of human
embryo implantation.
References
1.
2.
3.
4.
5.
6.
7.
B. C. Paria et al., Science 296, 2185 (2002).
O. D. Genbacev et al., Science 299, 405 (2003).
R. Alon, S. Feigelson, Semin. Immunol. 14, 93 (2002).
J. E. Smolen et al., J. Biol. Chem. 275, 15876 (2000).
B. A. Lessey et al., J. Clin. Invest. 90, 188 (1992).
S. D. Spandorfer et al., Fertil. Steril. 77, 1209 (2002).
O. Genbacev, Y. Zhou, J. W. Ludlow, S. J. Fisher, Science
277, 1669 (1997).
www.sciencemag.org
CREDIT: PRESTON MORRIGHAN/SCIENCE
PERSPECTIVES