|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.
|Source:||eLIFE 6: (Journal)|
|Registered Authors:||Mullins, Mary C.|
|Keywords:||computational biology, developmental biology, stem cells, systems biology, zebrafish|
|PubMed:||28826472 Full text @ Elife|
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.
ABSTRACTA 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.