ZFIN ID: ZDB-PUB-170823-11
Systems biology derived source-sink mechanism of BMP gradient formation
Zinski, J., Bu, Y., Wang, X., Dou, W., Umulis, D., Mullins, M.
Date: 2017
Source: eLIFE   6: (Journal)
Registered Authors: Mullins, Mary C.
Keywords: computational biology, developmental biology, stem cells, systems biology, zebrafish
MeSH Terms:
  • Animals
  • Biophysical Phenomena
  • Body Patterning/physiology
  • Bone Morphogenetic Protein 2/metabolism
  • Bone Morphogenetic Proteins/antagonists & inhibitors
  • Bone Morphogenetic Proteins/metabolism*
  • Drosophila Proteins/metabolism
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/physiology
  • Glycoproteins/genetics
  • Glycoproteins/metabolism
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Models, Biological
  • Models, Theoretical
  • Morphogenesis
  • Mutation
  • Signal Transduction/physiology*
  • Smad5 Protein/metabolism
  • Systems Biology*
  • Zebrafish/embryology*
  • Zebrafish/growth & development
  • Zebrafish Proteins/metabolism*
PubMed: 28826472 Full text @ Elife
A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development.