Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning

Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis. The limb bud is patterned by crosstalk between the mesoderm and the overlying apical ectodermal ridge, but it has been difficult to determine the requirement for different ligands in this process. Here the authors use a chick wing explant system to show that fibroblast growth factors trigger a mesodermal programme that is key for timing limb bud patterning.

Automated summary

This study demonstrates the important role of fibroblast growth factors in triggering a mesodermal program that is essential for the timing of limb patterning. Additionally, it uncovers additional functions of Fgf signaling in maintaining gene expression and suppressing muscle development.