[P242]: The role of metalloproteinase ADAM10 in the embryonic visual system of Xenopus laevis

In Xenopus laevis embryos, retinal ganglion cell (RGC) axons leave the eye and navigate through the developing brain to their target, the optic tectum. There are a number of key decision points along this trajectory and we are particularly interested in one of them: the mid-diencephalon where RGC axons take a 45◦ angle caudal turn, directing them towards the optic tectum. We have recently shown that fibroblast growth factor 8 (FGF8) as well as members of the FGFR family (predominantly FGFR2 and FGFR4) are expressed in the neuroepithelium just dorsal to this turn site, suggesting that FGF8 may be signalling to FGFRs in the neuroepithelium in order to stimulate the production of an important guidance factor for axons in the developing optic tract. Furthermore, we have found that application of an FGF receptor (FGFR) inhibitor, SU5402, to the developing optic tract and neuroepithelium in an in vivo preparation results in RGC axon stalling at the turn in the mid-diencephalon. This suggests that FGF signalling is required for RGC axons to navigate this turn. Previously it was shown that members of the LIM homeodomain transcription factor (xLhx) family are expressed in the dorsal diencephalon (Bachy et al., 2001). Interestingly we found that exposure to the FGFR inhibitor, SU5402, in addition to causing RGC axons to stall, led to a downregulation in the expression of xLhx9 in the dorsal diencephalon. Since Lhx genes regulate the expression of a number of different guidance cues (Seth et al., 2006), we hypothesize that FGF signalling is required for the expression of xLhx9, which in turn regulates the expression of a guidance factor required to guide RGC axons through the turn in the mid-diencephalon. This idea will be tested in the future.