Systems biology derived source-sink mechanism of BMP gradient formation

• Main Authors: Joseph Zinski, Ye Bu, Xu Wang, Wei Dou, David Umulis, Mary C Mullins
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-08-01
• Series: eLife
• Subjects: BMP signaling; mathematical model-based computational screens; quantitative analysis; BMP diffusion; BMP shuttling; counter-gradient
• Online Access: https://elifesciences.org/articles/22199

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.