Hypothetical role of semaphorin class 4 in eye and pronephros development of Xenopus laevis

The translation initiation factor Eif6 is implicated in the regulation of ribosome assembly, selective mRNA translation, apoptosis and is probably part of the RNA-induced silencing complex (RISC). In Xenopus embryos eif6 overexpression causes aberrant eye and kidney development. gipc2 (GAIP interacting protein, C terminus, a PDZ-domain containing protein) morphants have eye and kidney phenotypes similar to that of the eif6 overex-pressors. eif6 interacts with igf receptor (igfr) activating akt pathway as well as with gipc2, which also binds to igfr (Booth at al. 2002). gipc2 protein is a powerful modulator of signals as it interacts with a variety of molecules implicated in cell signalling, such as semaphorins-F and -4C (Wang et al., 1999). We show that the interaction between eif6 and gipc2, requires gipc2-PDZ domain. In contrast to gipc2 w.t, gipc2-mutated in PDZ did not fully recovered eif6 gain-of-function effects in embryos, suggesting that gipc2 may bind through the PDZ domain not only to eif6, but also to additional partners implicated in the eye formation. Semaphorins are major regulators of morphogenesis involved in a variety of processes mainly related to the nervous system. Class 4 semaphorins have a PDZ binding site and, in particular, sema 4C and sema 4G, are expressed in eyes and pronephroi (Koestner et al. 2008). Here we show that the sema 4C or sema 4G morpholino injection in one blastomere of stage 2 embryo, realize aberrant phenotypes of eyes and pronephroi with a reduction of specific markers, suggesting a role for semaphorins in the formation of the two organs. Altogether, we hypothesize that eif6 iperexpression modifies the expression of gipc2 which in turn acts on semaphorins altering eyes and pronephroi developing pattern, both depending upon the igf signaling.