Eph Receptor Tyrosine Kinases and Their Ligands in Development 161
9.6 Cardiovascular Development
Blood vessels form de novo from a dispersed population of endothelial
cells in a process called vasculogenesis, which occurs in several independent locations during embryonic and extraembryonic development.
Subsequently, in angiogenesis, the network of thin tubules is further
differentiated into larger, branched vessels through a series of morphogenetic events involving sprouting, splitting and remodelling (Risau and
Flamme 1995; Risau 1997). Members of the Eph family have now been
implicated in the latter processes (Pandey et al. 1995; Yancopoulos et al.
1998; Adams et al. 1999; Wang et al. 1999).
Initially a clear-cut complementary expression pattern of Eph receptors and ligands was reported, in that EphrinB2 marks arterial, but not
venous endothelial cells from the onset of angiogenesis and, conversely,
a prominent receptor of EphrinB2, EphB4, marks veins, but not arteries
(Wang et al. 1999). Analysis of EphrinB2 knockout mice revealed
defects in angiogenesis of both arteries and veins leading apparently to
an early lethality, suggesting that Eph-family mediated reciprocal signaling between these two types of vessels is crucial for morphogenesis
of the capillary system. However, this more simplistic view has been
challenged by another investigation (Adams et al. 1999), which shows a
complex involvement of Eph family members, in that a number of Eph
receptors and ligands of the B-class are coexpressed on veins and
arteries in at least partially overlapping expression patterns. Also, intersomitic vessels that form at somite boundaries express EphB receptors,
while EphrinB2 is expressed in the caudal half of the somites. In the
EphrinB2 knockout mice, these vessels show an abnormal sprouting
behavior (Adams et al. 1999). These initial data suggest a prominent
role of the Eph family in angiogenesis.
Interestingly, since Ephrins and Eph receptors have been found to be
expressed in a variety of different tumors and tumor cell lines (Wicks et
al. 1992; Kiyokawa et al. 1994; Soans et al. 1994), it is possible that
these molecules are also involved in the process of neovascularization of
growing tumors. With this possibility in mind, it might be worthwhile to
investigate whether there is any link between metastasis, on the one
hand, and the Eph family controlling cell migration, on the other hand.
9.6 Cardiovascular Development
Blood vessels form de novo from a dispersed population of endothelial
cells in a process called vasculogenesis, which occurs in several independent locations during embryonic and extraembryonic development.
Subsequently, in angiogenesis, the network of thin tubules is further
differentiated into larger, branched vessels through a series of morphogenetic events involving sprouting, splitting and remodelling (Risau and
Flamme 1995; Risau 1997). Members of the Eph family have now been
implicated in the latter processes (Pandey et al. 1995; Yancopoulos et al.
1998; Adams et al. 1999; Wang et al. 1999).
Initially a clear-cut complementary expression pattern of Eph receptors and ligands was reported, in that EphrinB2 marks arterial, but not
venous endothelial cells from the onset of angiogenesis and, conversely,
a prominent receptor of EphrinB2, EphB4, marks veins, but not arteries
(Wang et al. 1999). Analysis of EphrinB2 knockout mice revealed
defects in angiogenesis of both arteries and veins leading apparently to
an early lethality, suggesting that Eph-family mediated reciprocal signaling between these two types of vessels is crucial for morphogenesis
of the capillary system. However, this more simplistic view has been
challenged by another investigation (Adams et al. 1999), which shows a
complex involvement of Eph family members, in that a number of Eph
receptors and ligands of the B-class are coexpressed on veins and
arteries in at least partially overlapping expression patterns. Also, intersomitic vessels that form at somite boundaries express EphB receptors,
while EphrinB2 is expressed in the caudal half of the somites. In the
EphrinB2 knockout mice, these vessels show an abnormal sprouting
behavior (Adams et al. 1999). These initial data suggest a prominent
role of the Eph family in angiogenesis.
Interestingly, since Ephrins and Eph receptors have been found to be
expressed in a variety of different tumors and tumor cell lines (Wicks et
al. 1992; Kiyokawa et al. 1994; Soans et al. 1994), it is possible that
these molecules are also involved in the process of neovascularization of
growing tumors. With this possibility in mind, it might be worthwhile to
investigate whether there is any link between metastasis, on the one
hand, and the Eph family controlling cell migration, on the other hand.