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. 2012 Jun 27;1(8):775–788. doi: 10.1242/bio.20121339

Fig. 6. Mutants affecting smooth muscle formation can be reproduced.

Fig. 6.

(A) Distribution of smooth muscles (thermal colormap) and FGF10 (black contours) in different mutants. WT: smooth muscles appear between FGF10 spots. FGF9−/− mutant: setting FGF9 production rate to 0 leads to ectopic smooth muscles at the tip of the growing bud and more smooth muscles in proximal regions. Overexpression of FGF9 in the distal epithelium: FGF9 was produced in the mesothelium at rate ρI (as in WT) and simultaneously in the epithelium at rate 3×ρI (overexpression). This leads to a complete block of smooth muscle expression. Hypomorphic FGF10 mutant: when Fgf10 expression is reduced to 45%, smooth muscle intensity is reduced. The distance between branching points is increased (see D). Fgfr2c+/Δ mutant: Mesenchymal cells express both Fgfr2c (responding to FGF9, as in WT) and Fgfr2b (responding to FGF10, usually only in the epithelium). Instead of responding to the FGF9 concentration, mesenchymal cells now respond to the FGF9 plus FGF10 concentration. Smooth muscles are only slightly reduced (from 2.6 to 2) and patterning (FGF10 spots) could be observed only in proximal areas. Fgfr2c+/Δ; Fgf10+/− mutant: in order to compensate the effect of the mutation Fgfr2c+/Δ, one of the two alleles of Fgf10 was deleted. Reducing FGF10 production rate two-fold, in addition to modifications for Fgfr2c+/Δ, restores the patterning of FGF10. (B) Expression levels (integral of the production term over the surface) of Fgf10, Shh and Ptc for all mutants. (C) SM concentration (integral of SM concentration over the surface) for all mutants. (D) Behavior of the allelic series for Fgf10. FGF10 production rate was stepwise decreased from 100% of WT to 30% of WT. The distance between two branching points is reported for each simulation. If FGF10 production rate is more than 50% of WT, the interbud distance is approximately constant. All simulations are shown at τ = 120. For simplicity, we kept for all mutants the same value for vg as in WT. All parameters are as in Table 1 unless otherwise stated.