EphA7 regulates claudin6 and pronephros development in Xenopus

Highlights: • EphA7 knockdown perturbs pronephros morphogenesis and differentiation in Xenopus. • Knockdown of EphA7 reduces membrane CLDN6 level in the pronephros tubule cells. • EphA7 phosphorylates and destabilizes membrane CLDN6 in cultured cells. • A soluble form of EphA7 stabilizes CLDN6 and antagonizes EphA7. Eph/ephrin molecules are widely expressed during embryonic development, and function in a variety of developmental processes. Here we studied the roles of the Eph receptor EphA7 and its soluble form in Xenopus pronephros development. EphA7 is specifically expressed in pronephric tubules at tadpole stages and knockdown of EphA7 by a translation blocking morpholino led to defects in tubule cell differentiation and morphogenesis. A soluble form of EphA7 (sEphA7) was also identified. Interestingly, the membrane level of claudin6 (CLDN6), a tetraspan transmembrane tight junction protein, was dramatically reduced in the translation blocking morpholino injected embryos, but not when a splicing morpholino was used, which blocks only the full length EphA7. In cultured cells, EphA7 binds and phosphorylates CLDN6, and reduces its distribution at the cell surface. Our work suggests a role of EphA7 in the regulation of cell adhesion during pronephros development, whereas sEphA7 works as an antagonist.