An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation

摘要: ABSTRACT The signal-induced proliferation-associated family of proteins comprises four members, SIPA1 and SIPA1L1-3. Mutations the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes lenses including lens fiber cell maturation defects. We found direct interaction between Epha4, building functional platform for proper ocular development. Epha4 deficiency phenocopied rescue experiments demonstrated acts upstream during development, with both required early specification. phenotype, upon either or Sipa1l3, partially mediated rax. demonstrate canonical Wnt signaling is inhibited downstream normal Depletion resulted an upregulation axin2 expression, Wnt/β-catenin target gene. line this, depletion could be rescued blocking activating non-canonical signaling. therefore conclude this pathomechanism prevents development cells, resulting