Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2
in Caenorhabditis elegans
Akira Nukazuka,
Hajime Fujisawa,
Toshifumi Inada,
Yoichi Oda,, and
Shin Takagi1
Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-8602, Japan
Abstract:
Conserved semaphorin–plexin signaling systems govern various aspects of animal development, including axonal guidance in vertebrates and epidermal morphogenesis in Caenorhabditis elegans. Here we provide in vivo evidence that stimulation of mRNA translation via eukaryotic initiation factor 2
(eIF2) is an essential downstream event of semaphorin signaling in C. elegans. In semaphorin/plexin mutants, a marked elevation in the phosphorylation of eIF2 is observed, which causes translation repression and is causally related to the morphological epidermal phenotype in the mutants. Conversely, removal of constraints on translation by genetically reducing the eIF2 phosphorylation largely bypasses requirement for the semaphorin signal in epidermal morphogenesis. We also identify an actin-depolymerizing factor/cofilin, whose expression in the mutants is predominantly repressed, as a major translational target of semaphorin signaling. Thus, our results reveal a physiological significance for translation of mRNAs for cytoskeletal regulators, linking environmental cues to cytoskeletal rearrangement during cellular morphogenesis in vivo.
Key Words: C. elegans • cofilin • eIF2 • epidermal morphogenesis • mRNA translation • semaphorin]
Received for publication December 18, 2007.
Accepted for publication February 27, 2008.
1 Corresponding author.
E-MAIL i45116a{at}nucc.cc.nagoya-u.ac.jp; FAX 81-52-789-2979.
Supplemental material is available at http://www.genesdev.org.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1644008.
