Semaphorins comprising a protein family in animals regulate diverse developmental events, and plexins serve as semaphorin receptors to transduce the signals into cytoskeletal reorganization. Genetic analysis has revealed that the semaphorin/plexin system regulates epidermal morphogenesis in C. elegans: in semaphorin (smp) and plexin (
plx-1) mutants, epidermal cells in the larval male tails are aberrantly arranged, which results in an ectopic positioning of sensory ray 1 in the adult stage. We here report on in vivo evidence that mRNA translation is stimulated by SMP - PLX-1 signal via reduced phosphorylation of a translational regulator, eukaryotic initiation factor 2<font face=symbol>a</font> (eIF2<font face=symbol>a</font>). Higher phosphorylation of eIF2<font face=symbol>a</font>, which was observed in smp /
plx-1 mutants, reduced to the normal level by restoring the SMP - PLX-1 signal, implying that this signal is necessary to lower the eIF2<font face=symbol>a</font> phosphorylation. Overexpression of a phosphomimetic eIF2<font face=symbol>a</font>, as well as inactivation of translation machineries (eIF2<font face=symbol>a</font>, eIF2<font face=symbol>b</font>, eIF4G), produced the ray phenotype comparable to smp /
plx-1 mutants, indicating that downregulated protein synthesis is attributed to the ray defect in mutants. On the other hand, lowered eIF2<font face=symbol>a</font> phosphorylation caused by the loss-of-function mutations in GCN1 and PEK/PERK, both of which normally inhibit mRNA translation by participating in the eIF2<font face=symbol>a</font> phosphorylation, suppressed the ray phenotype in smp /
plx-1 mutants, suggesting that enhanced protein synthesis is sufficient for SMP - PLX-1 signaling. Thus, these data demonstrate an essential role for translation stimulation mainly via reduced eIF2<font face=symbol>a</font> phosphorylation in SMP-induced proper epidermal ray morphogenesis. In our current research, we aim to identify target protein(s) that is synthesized in response to the SMP - PLX-1 signal. In this meeting, we will also make a progress report on this issue and further discuss the mechanism of cytoskeletal reorganization during the semaphorin/plexin-mediated cellular morphogenesis.