Fig. 10. Proposed models for Gas1 action and Fgf10 regulation in the developing limb. At the early phase of limb formation, Gas1 is not required for Fgf10/Fgf8 expression in the proximal mesenchyme and the AER, respectively (left). In the wild type (wt), Gas1 is expressed in the anterior two-thirds of the mesenchyme, Fgf10 in a large contiguous domain of the limb mesenchyme composed of a proximal and a distal domain, and Fgf8 in the AER. In the Gas1 mutant, Fgf10 expression is lacking at the distal domain, Fgf8 is not maintained and the AER is thinner (bottom panel). Our FGF10 rescue injection data indicate that FGF10 at the distal mesenchyme is continuously required to maintain Fgf8 expression (black arrow). We propose that Fgf10 expression in the distal mesenchyme is either directly regulated by Gas1 and AER Fgf8, in parallel (red arrows; model a) or by Fgf8 in the AER through a pathway that requires Gas1 activity (converged red arrow; model b). We also propose that the proximal domain of Fgf10 expression can be maintained (purple arrow) by Fgf4, 9 and 17 in the posterior AER in the absence of Fgf8. Fgf8 may also contribute to this regulation normally. The color code for each gene expression domain is at the right bottom corner.

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