Soh2020 - Spatio-temporal morphogen gradient and BMP signaling
This model couples BMP morphogen gradient formation with Smad signaling in zebrafish and reproduces Fig.3B of the referenced paper. mBMP4 diffuses and forms a morphogen gradient in the host tissue where differential signal transduction kinetics for pSmad2 versus pSmad5 lead to narrow (pSmad2) versus wide (pSmad5) signal activity ranges in response to the same morphogen gradient (mBMP4) as input. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (https://morpheus.gitlab.io) to simulate the time course (movie) of the spatio-temporal dynamics. Further optional plots of the radial solution profile and the time courses of mean concentrations over the domain are included and temporarily inactivated in the model file, in section Analysis.
- Integration of Nodal and BMP Signaling by Mutual Signaling Effector Antagonism.
- Soh GH, Pomreinke AP, Müller P
- Cell reports , 4/ 2020 , Volume 31 , Issue 1 , pages: 107487 , PubMed ID: 32268105
- Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Max-Planck-Ring 9, 72076 Tübingen, Germany.
- Opposing sources of bone morphogenetic protein (BMP) and Nodal signaling molecules are sufficient to induce the formation of a full axis in zebrafish embryos. To address how these signals orchestrate patterning, we transplant sources of fluorescently tagged Nodal and BMP into zebrafish embryos, robustly inducing the formation of secondary axes. Nodal and BMP signal non-cell-autonomously and form similar protein gradients in this context, but the signaling range of Nodal (pSmad2) is shorter than the BMP range (pSmad5). This yields a localized region of pSmad2 activity around the Nodal source, overlapping with a broad domain of pSmad5 activity across the embryo. Cell fates induced in various regions stereotypically correlate with pSmad2-to-pSmad5 ratios and can even be induced BMP- and Nodal-independently with different ratios of constitutively active Smad2 and Smad5. Strikingly, we find that Smad2 and Smad5 antagonize each other for specific cell fates, providing a mechanism for how cells integrate and discriminate between overlapping signals during development.
|BMP_signaling.xml||MorpheusML representation of spatio-temporal BMP signaling model.||10.88 KB||Preview | Download|
|Soh2020_Fig3B.png||Published Fig.3B (CC BY-NC-ND 4.0) by Soh et al., using the simulator COMSOL.||205.10 KB||Preview | Download|
|BMP_signaling.png||PNG plot of model using the simulator Morpheus v2.2.||65.60 KB||Preview | Download|