Supplementary Materials

Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients

J. Raspopovic, L. Marcon, L. Russo, J. Sharpe

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • Materials and Methods
  • Supplementary Text
  • Figs. S1 to S8
  • Captions for movies S1 to S14
  • References
Microarray data
Microarray data, accessible through GEO Series accession no. GSE58158

Images, Video, and Other Other Media

Movie S1
The patterning dynamics of the micromass culture obtained with Sox9-EGFP autopod cells compared against the dynamics of the simulation of Turing mechanism (A simple linear model of a Substrate- depleted mechanism with two molecules).
Movie S2
Micromass culture initiated with Sox9-negative cells FACS-sorted from Sox9-EGFP autopods, the video shows 22h of culture. A periodic spatial pattern is formed by spatially-controlled Sox9 up-regulation.
Movie S3
Micromass culture initiated with Sox9-positive cells FACS-sorted from Sox9-EGFP autopods, the video shows 22h of culture. A periodic spatial pattern is formed by spatially-controlled Sox9 down-regulation.
Movie S4
Simulated concentration of Sox9 (high values in red) when the BSW model is simulated inside the limb growing model. The PD expansion that underlies limb elongation orients the stripes along the PD axis.
Movie S5
Simulated concentration of Sox9 (high values in red) when the activity of the BSW model is restricted to the autopod region by the experimental expression patterns of Hoxd13. A stereotypical pattern is formed thanks to the progressive expansion of Hoxd13 into the anterior and the proximal part of the limb which stimulate a reproducible spatial configuration of the Turing pattern. In later timepoints, distal stripe bifurcations are observed due to the geometry of the limb.
Movie S6
Simulated concentration of Sox9 (high values in red) when the activity of the BSW model is modulated by Fgf signaling to increase the wavelength and align the stripes. Stripe bifurcations are prevented and the pattern orients radially towards the AER.
Movie S7
Simulated concentration of Sox9 (high values in red) and Bmp (high values in green) when the activity of the BSW model is modulated by Fgf signaling and Hoxd13. A reproducible pattern that captures the main features of the experimental expression patterns of Sox9 is obtained.
Movie S8
Simulated concentration of Sox9 (high values in white), experimental expression pattern of Hoxd13 (high values in red) and Fgf signaling (high values in green). Spatio-temporal dynamics that robustly reflect the experimental expression patterns of Sox9 are obtained by modulating the the BSW Turing model with the positional information provided by Fgf signaling and Hoxd13.
Movie S9
Sox9 concentrations (high values in red) in a simulation where addition of LDN was simulated by in- hibiting Bmp signaling. Similar to the experiment, Sox9 is down-regulated and the digit pattern is disrupted.
Movie S10
Sox9 concentrations (high values in red) in a simulation where addition of IWP2 (Wnt secretion inhibitor) was simulated by reducing the Wnt production term. Remarkably similar to the experimental situation, the Sox9 expression in the digits expands producing fusion of the digits.
Movie S11
22h of a Sox9-EGFP E11.5 limb culture with a Bmp2-soaked bead (dark circle) implanted in the autopod region.
Movie S12
Simulated concentration of Sox9 (high values in red) in a virtual Bmp-bead experiment. The virtual Bmp bead (white triangles) is implanted at E11.5.
Movie S13
22h of a Sox9-EGFP E11.5 limb culture with aWnt3a-soaked bead (dark circle) implanted in the autopod region.
Movie S14
Simulated concentration of Sox9 (high values in red) in a virtual Wnt-bead experiment. The virtual Wnt bead (white triangles) is implanted at E11.5.