Gtpbp2 is required for BMP signaling and mesoderm patterning in Xenopus embryos

Abstract

Smad proteins convey canonical intracellular signals for activated receptors in the TGFβ superfamily, but the activity of Smads and their impact on target genes are further regulated by a wide variety of cofactors and partner proteins. We have identified a new Smad1 partner, a GTPase named Gtpbp2 that is a distant relative of the translation factor eEf1a. Gtpbp2 affects canonical signaling in the BMP branch of the TGFβ superfamily, as morpholino knockdown of Gtpbp2 decreases, and overexpression of Gtpbp2 enhances, animal cap responses to BMP4. During Xenopus development, gtpbp2 transcripts are maternally expressed and localized to the egg animal pole, and partitioned into the nascent ectodermal and mesodermal cells during cleavage and early gastrulation stages. Subsequently, gtpbp2 is expressed in the neural folds, and in early tadpoles undergoing organogenesis gtpbp2 is expressed prominently in the brain, eyes, somites, ventral blood island and branchial arches. Consistent with its expression, morpholino knockdown of Gtpbp2 causes defects in ventral–posterior germ layer patterning, gastrulation and tadpole morphology. Overexpressed Gtpbp2 can induce ventral–posterior marker genes and localize to cell nuclei in Xenopus animal caps, highlighting its role in regulating BMP signaling in the early embryo. Here, we introduce this large GTPase as a novel factor in BMP signaling and ventral–posterior patterning.