Organizer-derived Bmp2 is required for the formation of a correct Bmp activity gradient during embryonic development

Nat Commun. 2014 Apr 29:5:3766. doi: 10.1038/ncomms4766.

Abstract

Bone morphogenetic proteins (Bmps) control dorsoventral patterning of vertebrate embryos through the establishment of a ventrodorsal gradient of the activated downstream cytoplasmic effectors Smad1/5/8. Some Bmp ligands are expressed in the ventral and lateral regions and in the organizer during gastrulation of the embryo, but it remains unclear how organizer-derived Bmps contribute to total Bmp ligand levels and to the establishment of the correct phospho-Smad1/5/8 gradient along the ventrodorsal axis. Here we demonstrate that interference with organizer-specific Bmp2b signalling in zebrafish embryos alters the phospho-Smad1/5/8 gradient throughout the ventrodorsal axis, elevates the levels of the Bmp antagonist Chordin and dorsalizes the embryos. Moreover, we show that organizer-derived Bmp2b represses chordin transcription in the organizer and contributes to the control of the Chordin gradient. Combining these experimental results with simulations of Bmp's reaction-diffusion dynamics, our data indicate that organizer-produced Bmp2b is required for the establishment and maintenance of a Bmp activity gradient and for appropriate embryonic dorsoventral patterning during gastrulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Body Patterning / physiology*
  • Bone Morphogenetic Protein 2 / metabolism*
  • Chromatin Immunoprecipitation
  • DNA Primers / genetics
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental / physiology*
  • Glycoproteins / metabolism
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Luciferases
  • Microscopy, Confocal
  • Models, Biological*
  • Organizers, Embryonic / metabolism
  • Signal Transduction / physiology*
  • Smad Proteins / metabolism
  • Zebrafish / embryology*
  • Zebrafish Proteins / metabolism*

Substances

  • Bone Morphogenetic Protein 2
  • DNA Primers
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Smad Proteins
  • Zebrafish Proteins
  • bmp2b protein, zebrafish
  • chordin
  • Luciferases