Chemistry Reference
In-Depth Information
In parallel, the size and shape of the implanting conceptus, embryo- maternal
signaling and the mode of implantation in the uterus vary amazingly. In rumi-
nants and pigs, the blastocyst develops to a long fi lamentous structure. In contrast,
in horses, rabbits and carnivores, the implanting conceptus is by and large spheri-
cal. Depending on the species, embryonic secretions and/or oviduct and/or uterine
secretions form additional glycoprotein layers covering the inner and/or outer
surface of the ZP. In rabbits, for example, the ZP is covered by a thick layer of
highly sulfated mucoproteins produced by the oviduct epithelium. In horses, the
blastocyst (Figure 24.4) produces a glycoprotein capsule mainly composed of
mucin-like glycoproteins beneath the ZP as a prerequisite for further develop-
ment. This capsule replaces the ZP to enclose the conceptus during the second
and third weeks of pregnancy.
Notably, glycans are not only a central component of the ZP and additional gly-
coprotein coats around the embryo. Later on, cell surface glycans are crucial for
proper embryo implantation in the uterus, in the right place at the right time. Both
the trophoblast of the conceptus and the uterine luminal epithelium (ULE) are
covered by a glycocalyx. The surface of the nonreceptive ULE has a high density
of transmembrane mucins such as MUC1 precluding implantation (for informa-
tion on mucins, please see Chapter 7.5). Uterine receptivity appears to go along
with a loss of MUC1 and a remodeling of the glycocalyx of the ULE [10]. At least
equally important and an arising matter is that cell-surface glycans appear to be
critically involved in the maintenance and development of embryonic stem cells.
24.8
Surface Glycans of Stem Cells
Stem cells are the 'master cells' of the organisms, since they can both renew
themselves through mitotic cell division and generate a progeny of specialized
cells. They constitute the basis for tissue formation, regeneration and repair. Stra-
tegically presented at the cell surface, glycans are suitably positioned to be involved
in the control of stem cell maintenance, proliferation and differentiation, for
instance by modulating structure- activity profi les of signaling molecules (for
examples how glycosylation changes growth factor receptor parameters, please see
Table 25.3) [11]. Regulation of growth and differentiation factors can, for instance,
be exerted through the following effector routes: (i) Fibroblast growth factor ( FGF ) 2
is a key player in regulating self-renewal and proliferation of stem cells. FGFs bind
to both high-affi nity FGF receptors and heparan sulfate proteoglycans at the cell
surface, whose affi nity is regulated by the pattern of substitutions such as sulfation
(for information on proteoglycans, please see Chapter 11 and Chapter 22.6).
(ii) Wnt proteins are secreted glycoproteins associated with the extracellular matrix,
which induce intracellular signaling. Matrix contact is mediated by heparan sulfate
proteoglycans. (iii) Notch is a large single-pass transmembrane glycoprotein essen-
tial for development by its regulatory function in stem cell fate determination.
Notch signaling depends on glycosylation of extracellular epidermal growth factor
