Eph Receptors and Ephrins Are Key Regulators of Morphogenesis 135
Recent results in the zebrafish embryo show that a similar process,
based on the expression of alternating stripes of Eph receptors and
ephrins, is important for normal somite segmentation to occur. Several
Eph receptors and ephrins are expressed in the somitic mesoderm in a
number of vertebrate species (Bergemann et al. 1995; Cooke et al. 1997;
Flenniken et al. 1996; Gale et al. 1996; Scales et al. 1995). Using a
dominant-negative strategy of injecting RNA encoding kinase-inactive
receptors or soluble ephrins into the zebrafish embryo, it has been
shown that Eph receptor/ephrin signalling is required for normal somite
segmentation (Durbin et al. 1998). As in the hindbrain rhombomeres,
boundaries in the paraxial mesoderm are misplaced or absent in experimental embryos.
There is an important difference between the spatial arrangement of
Eph receptor/ephrin expression in the somites and in the hindbrain. In
the latter, expression domains correspond to alternating rhombomeres,
but in the somites, expression domains of Eph receptor and ephrin
correspond to anterior and posterior halves of a single somite. Thus, in
the paraxial mesoderm a somite border forms at alternate interfaces
between receptor- and ligand-expressing cells. This is consistent with
grafting experiments in the chick embryo in which it was shown that
interfaces between anterior and posterior regions of the somite are
required for a boundary to form (Stem and Keynes 1987). It is of
considerable interest to know how these expression domains are controlled in the forming hindbrain and in the paraxial mesoderm. In the
hindbrain it is known that the EphA4 expression in rhombomeres 3 and
5 is under the control of the transcriptional regulator Krox-20 (Theil et
al. 1998). It is not yet clear how the dynamic expression of EphA4 and
ephrin-B2 is controlled in the unsegmented presomitic mesoderm.
In addition to its restricted expression in the hindbrain, EphA4 is also
expressed in distinct domains of the developing forebrain. Experiments
in which a dominant-negative form of EphA4 was overexpressed demonstrated a role for EphA4 in the regionalisation of this tissue (Xu et al.
1996). The zebrafish EphA4 homologue is expressed from early neural
plate stages in regions of the presumptive diencephalon that are fated not
to become eye tissue. As development proceeds, the eye fields come to
lie lateral to, and almost completely separate from, the diencephalon
except for the location of the eye stalk. EphA4 expression persists in the
ventral and dorsal diencephalic regions during these stages. In embryos
Recent results in the zebrafish embryo show that a similar process,
based on the expression of alternating stripes of Eph receptors and
ephrins, is important for normal somite segmentation to occur. Several
Eph receptors and ephrins are expressed in the somitic mesoderm in a
number of vertebrate species (Bergemann et al. 1995; Cooke et al. 1997;
Flenniken et al. 1996; Gale et al. 1996; Scales et al. 1995). Using a
dominant-negative strategy of injecting RNA encoding kinase-inactive
receptors or soluble ephrins into the zebrafish embryo, it has been
shown that Eph receptor/ephrin signalling is required for normal somite
segmentation (Durbin et al. 1998). As in the hindbrain rhombomeres,
boundaries in the paraxial mesoderm are misplaced or absent in experimental embryos.
There is an important difference between the spatial arrangement of
Eph receptor/ephrin expression in the somites and in the hindbrain. In
the latter, expression domains correspond to alternating rhombomeres,
but in the somites, expression domains of Eph receptor and ephrin
correspond to anterior and posterior halves of a single somite. Thus, in
the paraxial mesoderm a somite border forms at alternate interfaces
between receptor- and ligand-expressing cells. This is consistent with
grafting experiments in the chick embryo in which it was shown that
interfaces between anterior and posterior regions of the somite are
required for a boundary to form (Stem and Keynes 1987). It is of
considerable interest to know how these expression domains are controlled in the forming hindbrain and in the paraxial mesoderm. In the
hindbrain it is known that the EphA4 expression in rhombomeres 3 and
5 is under the control of the transcriptional regulator Krox-20 (Theil et
al. 1998). It is not yet clear how the dynamic expression of EphA4 and
ephrin-B2 is controlled in the unsegmented presomitic mesoderm.
In addition to its restricted expression in the hindbrain, EphA4 is also
expressed in distinct domains of the developing forebrain. Experiments
in which a dominant-negative form of EphA4 was overexpressed demonstrated a role for EphA4 in the regionalisation of this tissue (Xu et al.
1996). The zebrafish EphA4 homologue is expressed from early neural
plate stages in regions of the presumptive diencephalon that are fated not
to become eye tissue. As development proceeds, the eye fields come to
lie lateral to, and almost completely separate from, the diencephalon
except for the location of the eye stalk. EphA4 expression persists in the
ventral and dorsal diencephalic regions during these stages. In embryos