Biology Reference
In-Depth Information
Ephrin-regulated Contact
Repulsion of Growth Cones
Lene K. Harbott, Daniel J. Marston
and
Catherine D. Nobes
Eph receptor activation by membrane-tethered ephrin ligands is critical for
establishing correct neural projections, for creating boundaries between
tissues, and for patterning the developing vasculature. The intracellular signals
that regulate these diverse, cell contact-dependent biological responses are
largely unknown. We show that activation of two Eph receptors, EphB2 and
EphA7, by soluble ephrins stimulate the assembly of protrusive actin
structures (filopodia and lamellipodia) and contractile actin stress fibres in
Swiss 3T3 fibroblasts through the regulation of Rho GTPases. We have
examined actin structures and the morphology of retinal ganglion cell (RGC)
growth cones treated with soluble ephrin-A molecules. Ephrin-A5-Fc
treatment causes loss of the lamella of the RGC growth cone, and retraction
of the axon. The specific Rho kinase inhibitor, Y27632, prevents ephrin-
induced axon retraction, but not loss of growth cone lamella. Co-culturing
RGCs with fibroblasts expressing ephrin molecules on their surface allows us
to examine the dynamic responses triggered by Eph receptor-ephrin
interaction at sites of cell-cell contact. Besides growth cone collapse of the
neurons, we show that fibroblasts also respond to Eph-ephrin signalling by
lamella collapse at sites of contact and subsequent directional changes in
migration.
