PUBLICATION
Systems biology derived source-sink mechanism of BMP gradient formation
- Authors
- Zinski, J., Bu, Y., Wang, X., Dou, W., Umulis, D., Mullins, M.
- ID
- ZDB-PUB-170823-11
- 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
Citation
Zinski, J., Bu, Y., Wang, X., Dou, W., Umulis, D., Mullins, M. (2017) Systems biology derived source-sink mechanism of BMP gradient formation. eLIFE. 6.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping