controls the expression of gene(s) that are essential to recognize or to interpret
guidance cues that direct migrating muscle precursor cells to the limb buds.
Eph receptor signals during migration of muscle precursor cells
to the limbs
In addition to the above described genes characterized in my laboratory, other
researchers have reported that Eph receptors and their ligands affect
migration of muscle progenitor cells to the limb. In particular, when muscle
precursors delaminate from the dermomyotome and migrate into the forelimb
in the chick embryo, the EphA4 receptor tyrosine kinase and its ligand,
ephrin-A5, are expressed by muscle precursor cells and forelimb mesenchyme,
respectively. Ectopic expression of ephrin-A5 in the presumptive limb
mesoderm reduces the number of muscle precursor cells that reach the limb,
and the cells congregate abnormally near the lateral dermomyotome. In stripe
assays, isolated muscle precursor cells avoid substrate-bound ephrin-A5 and
this avoidance is abolished by addition of soluble ephrin-A5. Thus, ephrin-A5
appears to restrict the migration of muscle precursor cells to their appropriate
territories in the forelimb (Swartz et al., 2001).
In cell culture experiments, ligands of tyrosine kinase receptors with oncogenic
potential frequently affect not only growth but enhance cellular motility and act
as chemoattractants. The genetic analysis of such receptors and their ligands in
mice has demonstrated that they also control migration processes in vivo.
However, these studies cannot distinguish whether the receptors are required for
cell motility, or whether they provide directional cues and act as chemo-
attractants. So far, the best evidence that ligands of tyrosine kinase receptors can
provide chemoattractive cues comes from an genetic analysis in Drosophila,
where migrating border cells in the developing egg are guided by signals
provided by the Drosophila PDGF/VEGF and EGF receptor (Rorth, 2002).
Birchmeier, C. and Gherardi, E., 1998. Developmental roles of HGF/SF and its receptor,
the c-Met tyrosine kinase. Trends Cell Biol. 8(10): 404-410.
Bladt, F., Riethmacher, D., et al., 1995. Essential role for the c-met receptor in the
migration of myogenic precursor cells into the limb bud. Nature 376(6543): 768-771.