Neurite responses to ephrin-A5 modulated by BDNF: Evidence for TrkB–EphA interactions

In the developing visual system, growing retinal ganglion cell (RGC) axons are exposed to multiple guidance and growth factors. Furthermore, the relative levels of these factors are differentially regulated as topography is roughly established and then refined. We have shown that during the establishment of rough topography (P3), growth cones of pure and explanted RGCs treated with combinations of BDNF and ephrin-A5-Fc responded differently than RGCs treated with BDNF or ephrin-A5-Fc alone (p = 0.0083). The response to the combined treatment mimicked that of RGCs cultured with ephrin-A5-Fc alone once topography refines. The guidance cue receptors EphA and TrkB were shown to co-localise in RGCs in vitro. Furthermore, EphA and TrkB receptors interacted directly in in vitro binding assays. Our results suggest that the conversion of growth cone responses from collapse to stabilisation as topography refines, occurs as a result of interactions between EphA and TrkB receptors.