TRPP2-dependent Ca2++ signaling in dorso-lateral mesoderm is required for kidney field establishment in Xenopus

Abstract

In Xenopus laevis embryos, kidney field specification is dependent on retinoic acid (RA) and coincides with a dramatic increase of Ca2++ transients, but the role of Ca2++ signaling in the kidney field is unknown. Here, we identify TRPP2, a member of the transient receptor potential (TRP) superfamily of channel proteins encoded by the pkd2 gene, as a central component of Ca2++ signaling in the kidney field. TRPP2 is strongly expressed at the plasma membrane where it might regulate extracellular Ca2++ entry. Knockdown of pkd2 in the kidney field results in the downregulation of pax8, but not of other kidney field genes (lhx1, osr1 and osr2). We further show that inhibition of Ca2++ signaling with an inducible Ca2++ chelator also causes downregulation of pax8, and that pkd2 knockdown results in a severe inhibition of Ca2++ transients in kidney field explants. Finally, we show that disruption of RA results both in an inhibition of intracellular Ca2++ signaling and of TRPP2 incorporation into the plasma membrane of kidney field cells. We propose that TRPP2-dependent Ca2++ signaling is a key component of pax8 regulation in the kidney field downstream of RA-mediated nontranscriptional control of TRPP2.