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Fig. 8. Wnt and FGF signals interact to coordinate growth and cell fate
specification during limb development. In the newly established limb bud
(E9.5), both Wnt and FGF proteins signal throughout the limb mesenchyme and
maintain all cells in a multipotent, proliferative state (indicated by
red/blue hatching, marked by Axin2 and Dusp6). Following limb outgrowth, cells
in the center of the limb are no longer within range of the signals. This
allows cell cycle withdrawal and expression of Sox9, leading to establishment
of the chondrogenic core (indicated in blue, marked by Sox9). In the
periphery, meanwhile, cells out of range of FGFs from the AER are still within
range of Wnts from the ectoderm (indicated by red hatching, marked by Nbl1),
which maintains the proliferative state at a lower level, and respecifies the
cells towards soft connective tissue fates. As a result of these processes, a
proximodistally extended organ forms with a multipotent, rapidly growing tip
and a chondrogenic core surrounded by soft connective tissues.
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