|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online March 21, 2008
doi: 10.1242/10.1242/dev.018796
Meeting Review |
1 Materials Science Centre, The University of Manchester, Grosvenor Street,
Manchester M1 7HS, UK.
2 Centre for Molecular Medicine, Lab. 3.722 Stopford Building, Faculty of
Medical and Human Sciences, The University of Manchester, Manchester M13 9PT,
UK.
* Author for correspondence (e-mail: catherine.merry{at}manchester.ac.uk)
SUMMARY
The EMBO Workshop on Glycoscience and Development, organised by Philippe Delannoy, Yann Guérardel, Tony Merry and Jean-Claude Michalski, was held in the picturesque, contemplative environment of Les Minimes, a converted seventeenth century Flemish convent in Lille, France, in December 2007. A cross-section of researchers, both confirmed `glycomaniacs' and those newer to the field, discussed and debated recent advances in the field of glycobiology. Presentations ranged from the clinical applications of glycobiology to novel approaches for unravelling carbohydrate biosynthesis in developmental settings and models, such as the fruit fly, nematode and zebrafish.
Introduction
Glycoscience is the study of complex sugars, and of the molecules that display them and the proteins to which they bind. These post-translational modifications can be small and simple, such as the addition of a single sugar, e.g. O-linked N-acetylglucosamine (O-GlcNAc), or they can be very large and complex, as with modifications involving glycosaminoglycans, which can be more than 100 units in length and highly heterogeneous. Many complex sugars are attached to either proteins or lipids, which often tether them to cell surfaces, where they play key roles in cell recognition events, such as in inflammation, cancer and tissue patterning. The biosynthesis of glycoconjugates (the sugar and its protein/lipid moiety) requires the coordinated activity of a cohort of enzymes (including glycosyltransferases, epimerases, etc.), which work without a genetic template, and can create the myriad of structures that fulfil a variety of crucial functions, such as the biosynthesis of blood group antigens and the regulation of Notch signalling. Historically the preserve of a dedicated few, glycoscience is now a `hot' topic, both academically and commercially, and technological advances such as the generation of conditional knock-out animals and higher resolution structural studies have been key to this advance.
Throughout the meeting, a range of topics was covered, from which three
themes emerged: technological advances, evolutionary biology and development.
Technological advances are particularly welcomed, as, frequently, for a field
in which there is no method for template-driven amplification or for rapid
global sequencing, these lead to exciting and novel findings
(Merry and Merry, 2005
). As
discussed in more detail below, Ajit Varki (University of California, San
Diego, USA) provided an introduction to the second theme of evolutionary
biology, explaining how, `Nothing in Glycobiology makes sense, except in the
light of evolution' (Varki,
2006), which was followed by a wealth of supporting evidence. The
discussions of the role of glycoscience in development ranged from
fertilisation and implantation to the specifics of organ formation. Here, we
have predominantly focused on those presentations and themes that particularly
concern the many ways in which glycoscience affects development.
Technological advances
As mentioned above, technological advances in glycoscience have lead to
many exciting discoveries. Complex sugars are difficult to study using common
structural analytical tools, such as mass spectroscopy, as they are highly
heterogeneous and labile under ionising conditions. Jerry Hart (Johns Hopkins
Medical School, Baltimore, USA) explained how modified mass spectrometric
analyses, combined with enzymatic characterisation, have been of significant
benefit. This approach has enabled the discovery that O-GlcNAcylation
is much more widespread and dynamically regulated than was previously thought
(Hart et al., 2007),
re-enforcing the view that this modification is as important as
phosphorylation for the sensing of nutrient levels and stress within cells.
Similar problems with detection have previously restricted the analysis of
heparan sulphate (HS). However, as highlighted by Claire Johnson (University
of Manchester, Manchester, UK), a panel of phage-display-derived antibodies,
able to detect subtle differences in HS patterning, can be combined with flow
cytometry to characterise cell-surface HS in a rapid and non-destructive
manner (Johnson et al., 2007).
Another method introduced was that of high-resolution magic angle spinning
(HRMAS) NMR for the analysis of polysaccharides in an impure state. Described
enthusiastically by Guy Lippens (University of Lille, Lille, France) as a
`lousy' method (as it requires relatively large amounts of material), it is,
however, suited for complex biological samples, as it can generate data from
material without prolonged and wasteful purification steps. This allows
ingenious experiments to be undertaken, such as the analysis of live bacteria,
using pulse-chase with 13C to follow the biosynthesis of glycans as
the bacteria multiply (Hanoulle et al.,
2006). HRMAS NMR has also been used to study the prodrug
ethionamide, used for the treatment of multidrug-resistant tuberculosis,
helping to uncover its activation mechanism and to detect intermediates that
are unstable when removed from the cellular environment
(Hanoulle et al., 2006).
Glycoscience and evolution
Ajit Varki began his talk by explaining that humans can be considered as a
`knock-out model' for the function of a specific sugar modification, that of
N-glycolylneuraminic acid (Neu5Gc). This form of sialic acid is
widely expressed in mammals, including in great apes, but is not found in
humans because of an inactivating mutation in the gene
(CMP-N-acetylneuraminic acid hydroxylase) that is required to form
Neu5Gc from the related sialic acid Neu5Ac, a mutation that occurred in our
ancestors 
3 million years ago (Varki,
2007). These residues are often displayed at the termini of sugar
chains that act as receptors for a wide variety of binding proteins, such as
haemagglutinins, selectins and siglecs. Varki explained how pathogens to which
humans are selectively sensitive tend to preferentially bind the excess of
Neu5Ac (e.g. Plasmodium falciparum), whereas those that tend to
infect animals (e.g. E. coli K99), even when humans are in close
proximity, preferentially bind Neu5Gc. However, Neu5Gc can be found in human
cells and tissues, and in carcinomas, following its uptake from an extrinsic
source. Circulating antibodies against Neu5Gc are found in all normal adults,
which are very specific for these Neu5Gc-containing epitopes. This
antigen-antibody reaction is hypothesized to cause chronic inflammation and to
increase the risk of cancer and other diseases. This is of particular
significance because the levels of Neu5Gc to which we are exposed are already
high, and are likely to increase in the near future. For example, major
contributors are diet, with red meat and dairy products being particularly
high in Neu5Gc, and biotechnology products that have used animal cells and
sera as a source of Neu5Gc for metabolic uptake by cultured cells. This
discussion came as a timely reminder of the benefits of a vegan diet prior to
the serving of veal and crème caramel at lunch!
Continuing with the theme of glycoscience and evolution, and choosing the
provocative title of `How is a Worm more complex than a Fly', Iain Wilson
(Universität für Bodenkultur, Vienna, Austria) argued that major
advances in recent years have led to the generation of comprehensive genomic
information for a variety of species. However, our knowledge of the glycomic
repertoire of most organisms is far from complete. By comparing and
contrasting two familiar species, the fruit fly (Drosophila
melanogaster) and the nematode worm (Caenorhabditis elegans),
Wilson discussed the occurrence of both specific structures and, more
generally, the total number of discernable N-glycans in the two
species. Asparagine (N-)linked-glycans are structurally diverse,
ranging from the relatively simple high-mannose type to hybrid and complex
N-glycans. Synthesised within the endoplasmic reticulum and Golgi,
they participate in protein folding and, once displayed at their final
destination, they play essential roles, such as defining the circulatory
lifetime of hormones, tissue patterning during embryogenesis, immune function
and inflammation. Within the fly, a total of 42 discrete N-glycans
have been identified, with high mannose and truncated N-glycan
structures being the major contributors to the profile. Conversely, wild-type
worms have possibly 65 different structures, some of which remain uncertain
(Paschinger et al., 2008).
Therefore is the worm more complex, at least in terms of glycans, than the
fly? Wilson argues that this is evidence against the Victorian concept of the
`Great chain of being', leading from simplistic organisms to the more complex,
and that, in fact, diversity exists all the way along the chain.
This diversity can cause problems when investigating glycoconjugates,
particularly as genetically simple developmental model systems are often
sought-after, bypassing the problems of redundancy associated with complex
systems. Vlad Panin (Texas A&M University, Texas, USA) introduced us to
the benefits of Drosophila for the study of sialyltransferase
activity, as it encodes a single enzyme [DSiaT (ST6Gal - FlyBase)] (in place
of the twenty found in humans) that shares greatest homology with the ST6Gal
family of mammalian sialyltransferases. DSiaT is highly conserved among
distant species within the Drosophila genus, suggesting significant
evolutionary conservation of DSiaT-mediated functions. This is evident from
the study of DSiaT mutant flies, which reveal it to be required for the
development and function of the Drosophila central nervous system
(CNS); however, the relatively low level of sialylated glycans within the fly
CNS (Koles et al., 2007)
indicates that they might be serving highly specialised functions. In
particular, a possible link to memory was highlighted, with DSiaT expression
found in projection neurons, as well as in a subset of other types of neurons.
Panin also discussed the locomotor abnormalities, neuromuscular junction
morphology and other neurological phenotypes of DSiaT mutants, which further
indicate that DSiaT is indispensable for the development and function of the
Drosophila CNS.
Introducing us to his work with fantastic views of Chesapeake Bay, Gerardo
Vasta (University of Maryland Biotechnology Institute, Baltimore, USA) shared
his passion for both the basic functional aspects of galectins (a family of
β-galactoside-binding proteins) and environmental protection, targeted to
the restoration of oyster beds. Once again turning to model systems, Gerardo
initially explained how galectins in zebrafish (Danio rerio) have a
high homology with human galectins, in both their structure and their
carbohydrate-binding specificity. Using morpholino technology to isolate the
function of specific family members, he reported that the knock down of
Drgal-L2 (Lgals1l2 - Zebrafish Information Network) resulted in defects in
muscle fiber organization and tail morphology, supporting its potential roles
in directing cell-laminin interactions, and in the ability of the notochord
(where it is highly expressed) and its derived structures to respond to sonic
hedgehog (Shh) and Wnt. A second family member, Drgal-L4, with a similar
expression pattern, when knocked down together with Drgal-L2, produces a more
severe phenotype, with additional defects in heart and blood cell development.
It was therefore suggested that galectins within the developing notochord, by
binding to endogenous glycans, can regulate the correct patterning response of
cells within the adjacent tissues of the neural tube and somites, particularly
those requiring bone morphogenetic protein (BMP) and Wnt signalling, such as
heart and blood. Moving to an invertebrate model system, the eastern oyster,
Gerardo also discussed the functional diversity of galectins, which in the
oyster also bind exogenous ligands, such as glycans on the microalgae they
feed upon, internalized by filtering litres of water per hour, which they
process by intrahaemocytic digestion. This activity, however, makes them
particularly susceptible to microbial pathogens and parasitic infections. One
parasite in particular, Perkinsus marinus, may have evolved its
surface carbohydrates to be strongly recognized by the oyster galectins
(Tasumi and Vasta, 2007). By
exploiting the role of galectin in recognising `non-self', it therefore gains
a selective advantage over the phytoplankton for infecting its oyster
host.
Glycoscience and early development
Introducing early mammalian development and the events surrounding
fertilisation, Pamela Stanley (Albert Einstein College of Medicine, New York,
USA) described how the large hydrodynamic volume occupied by membrane-tethered
glycans on glycoproteins and glycolipids makes them `The Molecular Frontier'
of the cell. One of the most critical frontiers encountered in development is
that of the zona pellucida (ZP), the complex extracellular matrix that
envelops mouse oocytes and ovulated eggs. In trying to dissect the role of
complex and hybrid N-glycans, core 1-derived O-glycans or
O-fucose glycans (see Fig.
1) in the function of the ZP, Stanley was faced with the problem
of tackling the compensatory effects of maternal transcripts. To overcome
this, maternal and zygotic mouse mutants were generated, by crossing floxed
alleles of Mgat1 (encoding N-acetylglucosaminyltransferase
I, essential for the hybrid and complex branching of N-glycans),
C1galt1 (encoding T-synthase, which transfers Gal to
O-GalNac to generate core 1 and 2 O-glycans) and
Pofut1 (encoding protein O-fucosyltransferase 1, which
transfers fucose to epidermal growth factor-like repeats) with ZP3-Cre mice.
Using this approach, Mgat1-/- eggs, decorated with
N-glycans that lack terminal Gal and GlcNAc, had previously been
generated and found to be developmentally compromised, but were readily
fertilised (Shi et al., 2004).
So to investigate the potential role of an alternative source of terminal Gal
and GlcNAc residues, the Stanley group generated
C1galt1-/- eggs, lacking core 1-derived O-glycans
(Williams et al., 2007). These
eggs were again fertilised, with embryos surviving to E13.5. In a
conclusive experiment, eggs lacking complex and hybrid N-glycans, as
well as core-1-derived O-glycans
(C1galt1-/-/Mgat1-/-) were generated
and again found to be fertile, thereby proving that terminal Gal or GlcNAc
residues on N- or O-glycans displayed by the zona pellucida
protein ZP3 are not essential for fertilisation. The experimental system also
allowed Stanley to demonstrate that, surprisingly, maternal and zygotic
Pofut1 mutant blastocysts develop normally, indicating that canonical
Notch signaling is not required for preimplantation development.
|
40%)
are karyotypically abnormal. Aplin described how, although these are observed
prior to implantation, the proportion found post-implantation is much lower,
suggesting that the process of implantation might itself select against
karyotypically abnormal embryos. A possible mechanism involves MUC1, a key
glycan-bearing component of the interface, which is present on the maternal
epithelium prior to implantation and is cleared from the site directly under
the embryo in humans. Aplin stressed how fertilisation and implantation
involve tightly orchestrated carbohydrate-mediated, long-lived and short-lived
cellular interactions (Aplin,
2006). For obvious reasons, these are particularly difficult to
study in humans, and Aplin described how in vitro model systems could be used
to provide valuable insights into these mechanisms.
Although membrane microdomains (or lipid rafts) and their role in cell-cell
interactions are relatively well investigated in development, the inclusion of
large numbers of glycolipids within these regions is frequently overlooked.
Ken Kitajima (Nagoya University, Nagoya, Japan) explained how a combination of
sugar-(specifically Lewis X glycans) and protein (cadherin)-mediated
interactions is required for blastodermal cell adhesion in medaka. Lipid rafts
are typically 50-200 nm in diameter and are a recognised `hot spot' for signal
transduction. When isolated from medaka embryos, these regions are enriched
for cholesterol and sphinomyelin, as well as for Lewis X-containing
glycoproteins and glycolipids. Also present are cadherin/catenin, Src and
phospholipase-C
, in agreement with previous studies that have shown
these domains to be involved in cell-cell interactions and in subsequent
signalling events. Using chemical methods to disrupt the structure of the
microdomains, Kitajima demonstrated that epiboly (the first cell migration
process that occurs from blastula to gastrula) depends on intact microdomains,
which can be reconstituted by adding cholesterol, which appears to allow the
re-integration of Lewis X-containing glycoproteins into the rafts
(Adachi et al., 2007). Kitajima
also analysed fucosyltransferase mutant animals, to investigate how
microdomains isolated from mutant medaka embryos interacted with each other.
By combining these genetic and chemical approaches, he concluded that
cell-cell binding during epiboly depends on both fucosylated carbohydrate and
protein components that reside within membrane microdomains. Indeed, the
Lex-glycoprotein and cadherin colocalise to the same microdomain,
although there are likely to be intermediate proteins associated with
them.
|
Once again the benefits of Drosophila as a model system for
helping to unravel the complexities of glycan biosynthesis were highlighted,
this time by Kelly Ten Hagen (NIH, Bethesda, USA), who investigated the
developmental role of mucin-type protein O-linked glycosylation
(Tian and Ten Hagen, 2007a).
An evolutionarily conserved family of UDP-N-acetylgalactosamine:
polypeptide N-acetylgalactosaminyltransferases (ppGaNTases in mammals
or PGANTs in Drosophila) initiate the formation of these glycans,
which occur in tightly regulated patterns during organ development. In
particular, high levels are observed along the apical and luminal surfaces of
developing tubular organs, suggesting a possible role in tubulogenesis. Using
a Drosophila pgant35A mutant, which has reduced levels of
O-glycans, Ten Hagen demonstrated the importance of
O-glycosylation for the organisation and polarisation of the cells
that comprise the tracheal tubes. Along with a substantial reduction in
O-glycans present, the pgant35A mutant has a severely
disrupted apical surface and apicobasal polarity within the tracheal system,
as well as loss of the diffusion barrier
(Fig. 2). Moving from
epithelial tube formation to another similarly highly evolutionarily conserved
process, that of cell adhesion, Ten Hagen introduced the pgant3
mutant, which displays a wing blister phenotype indicative of impaired
cell-cell interactions within the developing wing. Although integrins are
recognised as being a primary mediator of cell-matrix attachment during this
process, it appears that O-glycans are also involved, with
pgant3 mutants phenocopying other cell adhesion mutants. Crucially,
these systems provide a source of material to enable the proteins to which
these essential modifications are attached to be isolated and identified, an
ongoing interest of Ten Hagen's group.
The Ext1 mutant mouse, which lacks HS, dies early in embryonic
development prior to gastrulation. To study the role of HS in tissue
formation, and to try and uncover how this complex sugar co-ordinates growth
factor and morphogen signalling, as well as cell adhesion and migration, Yu
Yamaguchi (University of San Diego, San Diego, USA) uses a loxP-modified
conditional allele of Ext1 together with tissue-specific Cre drivers.
By ablating Ext1 with Nestin-Cre, he generated a mouse mutant with
multiple defects in brain patterning, including agenesis of the olfactory
bulbs, severe cerebral hypoplasia and the failed separation of the midbrain
and cerebellum. Mutant retinal axons are also misguided at the optic chiasm,
where a genetic interaction was demonstrated between the axon guidance ligand
Slit1 and Ext1, with HS being suggested to either increase the local
concentration of Slit1 or act as a co-receptor. To study these interactions in
more detail, the pathfinding of spinal cord commissural axons was analysed,
allowing the dissection of environmental and cell-autonomous effects
(Matsumoto et al., 2007). The
enzymatic or chemical removal of HS blocked axon outgrowth in response to
netrin 1, with further studies demonstrating that HS is additionally required
at the surface of responsive cells, indicating that, in the case of netrin 1,
HS is likely to acts as a co-receptor necessary for transducing netrin 1
signals. HS can therefore be an obligatory co-receptor or an essential
environmental factor that controls the distribution and degradation of
ligands, depending on developmental context. Moving from the brain to bone,
Yamaguchi also discussed recent findings from limb bud-targeted Ext1
knock-out mice. Loss of HS here causes severe limb bud hypoplasia with
multiple skeletal defects. The underlying cause of these defects appears to be
due to the aberrant differentiation and patterning of mesenchymal
condensations, which act as templates for cartilage. These data from
Ext1 conditional knock-out mice demonstrate that the role of HS in
regulating the function of diffusible factors during critical developmental
processes, so elegantly detailed in flies, is clearly also true in
mammals.
A frequent puzzle in glycoscience is the assignment of function to the
carbohydrate and non-carbohydrate elements of a glycoconjugate. The now common
use of knock-out and knock-down mutants has only confounded this issue with
specific glycan functions often remaining elusive. However, the function of
one glycan, polysialic acid, is now much clearer, thanks to the fascinating
work of Rita Gerardy-Schahn (Hannover Medical School, Hannover, Germany).
Polysialic acid (PolySia) is unusual, even amongst other carbohydrates, for
its high water-binding capacity and the large hydrodynamic volume it imparts
to the molecules to which it is attached. One of these in particular, neural
cell adhesion molecule (NCAM), dramatically switches from an adhesive molecule
to an anti-adhesive molecule following the addition of PolySia
(Hildebrandt et al., 2007).
During embryonic and early postnatal development of the mammalian brain, NCAM
and PolySia are both present at high levels. NCAM has been implicated in many
crucial developmental processes, including neuroblast migration, neurite
outgrowth and fasciculation, synaptogenesis and synaptic plasticity. However,
the NCAM knock-out mouse has an unexpectedly mild phenotype
(Cremer et al., 1994).
Conversely, mice mutant for two enzymes involved in PolySia biosynthesis,
ST8SiaIV and ST8SiaII, which have been generated by Gerardy-Schahn's lab, have
an unexpectedly severe (and lethal) phenotype, with retarded postnatal growth
and loss of the anterior commissure in the brain (despite the single mutants
having a mild phenotype). This, Gerardy-Schahn explains, is because the loss
of both ST8SiaV and ST8SiaII effectively causes a gain of PolySia-free NCAM
function. To test this, a triple knock-out mutant was generated by these
researchers that lacks both PolySia and NCAM. In these mice, anterior
commissure formation is normal. To further investigate this phenomenon, they
then performed experiments to vary the level of PolySia attached to NCAM.
These studies provided conclusive proof that the phenotype depends on the
amount of PolySia-free NCAM that is available and suggests that the system
generates NCAM only to then make it invisible by the addition of PolySia. It
was suggested that this process is essential for the plasticity that is
required during the complex process of building the vertebrate brain and
highlights the complex relationship between glycans and their `support act' -
the proteins and lipids to which they are attached.
Conclusion
This meeting was unique in both the subject area and the diverse interests of the participants. It therefore provided an ideal opportunity for newcomers to glycobiology and development to engage in discussion with others who had many years of experience in their respective fields. The engaging posters, particularly those presented by the younger scientists, provided a focus for these discussions and clearly demonstrated the diverse range of research interests. We left Les Minimes with our heads full of new ideas and opportunities for collaboration. Glycoscience may have previously been the domain of specialists but, certainly within developmental biology, this is unlikely to be the case in the future as the functions of these essential mediators of numerous and diverse cellular interactions - from signaling to adhesion - become clear.
REFERENCES
Adachi, T., Sato, C. and Kitajima, K. (2007).
Membrane microdomain formation is crucial in epiboly during gastrulation of
medaka. Biochem. Biophys. Res. Commun.
358,848
-853.[CrossRef][Medline]
Aplin, J. D. (2006). Embryo implantation: the
molecular mechanism remains elusive. Reprod. Biomed.
Online 13,833
-839.[Medline]
Cremer, H., Lange, R., Christoph, A., Plomann, M., Vopper, G.,
Roes, J., Brown, R., Baldwin, S., Kraemer, P. and Scheff, S.
(1994). Inactivation of the N-CAM gene in mice results in size
reduction of the olfactory bulb and deficits in spatial learning.
Nature 367,455
-459.[CrossRef][Medline]
Hanoulle, X., Wieruszeski, J. M., Rousselot-Pailley, P.,
Landrieu, I., Locht, C., Lippens, G. and Baulard, A. (2006).
Selective intracellular accumulation of the major metabolite issued from the
activation of the prodrug ethionamide in mycobacteria X. J.
Antimicrob. Chemother. 58,768
-772.
Hart, G. W., Housley, M. P. and Slawson, C.
(2007). Cycling of O-linked β-N-acetylglucosamine
on nucleocytoplasmic proteins. Nature
4461017
-1022.[CrossRef][Medline]
Hildebrandt, H., Mühlenhoff, M., Weinhold, B. and
Gerardy-Schahn, R. (2007). Dissecting polysialic acid and
NCAM functions in brain development. J. Neurochem.
103 Suppl. 1,56
-64.[CrossRef][Medline]
Johnson, C. E., Crawford, B. E., Stavridis, M., ten Dam, G.,
Wat, A. L., Rushton, G., Ward, C. M., Wilson, V., van Kuppevelt, T. H., Esko,
J. D. et al. (2007). Essential alterations in heparan
sulphate composition and distribution during the differentiation of embryonic
stem cells to neuroectodermal precursors. Stem Cells
25,1913
-1923.[CrossRef][Medline]
Koles, K., Lim, J. M., Aoki, K., Porterfield, M., Tiemeyer, M.,
Wells, L. and Panin, V. (2007). Identification of
N-glycosylated proteins from the central nervous system of Drosophila
melanogaster. Glycobiology
17,1388
-1403.
Matsumoto, Y., Irie, F., Inatani, M., Tessier-Lavigne, M. and
Yamaguchi, Y. (2007). Netrin-1/DCC signaling in commissural
axon guidance requires cell-autonomous expression of heparan sulfate.
J. Neurosci. 27,4342
-4350.
Merry, C. L. R. and Merry, A. H. (2005).
Glycoscience finally comes of age. EMBO Rep.
6, 900-903.[CrossRef][Medline]
Paschinger, K., Gutternigg, G., Rendi
, D. and Wilson, I.
B. H. (2008). The N-glycosylation of Caenorhabditis
elegans. Carbohydr. Res. (in press).
Shi, S., Williams, S. A., Seppo, A., Kurniawan, H., Chen, W.,
Ye, Z., Marth, J. D. and Stanley, P. (2004). Inactivation of
the Mgat1 gene in oocytes impairs oogenesis, but embryos lacking complex and
hybrid N-glycans develop and implant. Mol. Cell.
Biol. 24,9920
-9929.
Tasumi, S. and Vasta, G. R. (2007). A novel
galectin facilitates entry of the parasite Perkinsus marinus into
oyster hemocytes. J. Immunol.
179,3086
-3098.
Tian, E. and Ten Hagen, K. G. (2007a). O-linked
glycan expression during Drosophila development.
Glycobiology 17,820
-827.
Tian, E. and Ten Hagen, K. G. (2007b). A
UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is required for
epithelial tube formation. J. Biol. Chem.
282,606
-614.
Varki, A. (2006). Nothing in glycobiology makes
sense, except in the light of evolution. Cell
126,841
-845.[CrossRef][Medline]
Varki, A. (2007). Glycan-based interactions
involving vertebrate sialic acid-recognizing proteins.
Nature 446,1023
-1029.[CrossRef][Medline]
Williams, S., Xia, L., Cummings, R., McEver, R. and Stanley,
P. (2007). Fertilization in mouse does not require terminal
galactose or N-acetylglucosamine on the zona pellucida glycans J.
Cell Sci. 120,1341
-1341.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
