Small C-terminal Domain Phosphatase 3 Dephosphorylates the Linker Sites of Receptor-regulated Smads (R-Smads) to Ensure Transforming Growth Factor β (TGFβ)-mediated Germ Layer Induction in Xenopus Embryos

J Biol Chem. 2015 Jul 10;290(28):17239-49. doi: 10.1074/jbc.M115.655605. Epub 2015 May 26.

Abstract

Germ layer induction is one of the earliest events shortly after fertilization that initiates body formation of vertebrate embryos. In Xenopus, the maternally deposited transcriptional factor VegT promotes the expression of zygotic Nodal/Activin ligands that further form a morphogen gradient along the vegetal-animal axis and trigger the induction of the three germ layers. Here we found that SCP3 (small C-terminal domain phosphatase 3) is maternally expressed and vegetally enriched in Xenopus embryos and is essential for the timely induction of germ layers. SCP3 is required for the full activation of Nodal/Activin and bone morphogenetic protein signals and functions via dephosphorylation in the linker regions of receptor-regulated Smads. Consistently, the linker regions of receptor-regulated Smads are heavily phosphorylated in fertilized eggs, and this phosphorylation is gradually removed when embryos approach the midblastula transition. Knockdown of maternal SCP3 attenuates these dephosphorylation events and the activation of Nodal/Activin and bone morphogenetic protein signals after midblastula transition. This study thus suggested that the maternal SCP3 serves as a vegetally enriched, intrinsic factor to ensure a prepared status of Smads for their activation by the upcoming ligands during germ layer induction of Xenopus embryos.

Keywords: SCP3; SMAD transcription factor; Xenopus; embryo; germ layer induction; phosphatase; transforming growth factor beta (TGF-beta).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / metabolism
  • Animals
  • Binding Sites
  • Blastula / embryology
  • Blastula / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Female
  • Gastrula / embryology
  • Gastrula / metabolism
  • Gene Knockdown Techniques
  • Germ Layers / embryology
  • Germ Layers / metabolism
  • Ligands
  • Nodal Signaling Ligands / metabolism
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Smad Proteins, Receptor-Regulated / chemistry
  • Smad Proteins, Receptor-Regulated / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Xenopus Proteins / antagonists & inhibitors
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Ligands
  • Nodal Signaling Ligands
  • RNA, Messenger
  • RNA, Small Interfering
  • Smad Proteins, Receptor-Regulated
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • Activins
  • Phosphoprotein Phosphatases

Associated data

  • GEO/GSE68972