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Fig. 3. Representation of the signals required for forelimb initiation and
subsequent limb outgrowth in the mouse. Axial cues from the intermediate
mesoderm (IM) induce the expression of Tbx5 in the cells of the
lateral plate mesoderm (LPM) that will give rise to the forelimb (purple).
Tbx5 activates Fgf10, which in turn signals to the ectoderm
to induce Fgf8 in cells of the ectoderm (Ect) that will form the
apical ectodermal ridge (AER; shown in red)
(Agarwal et al., 2003). A
feedback loop is established as Fgf8 in the ectoderm positively
regulates Fgf10 in the limb mesenchyme. Establishment of the
Fgf10-Fgf8 positive-feedback loop is mediated by Wnt
signalling in the ectoderm, although this is not shown in the figure. Wnt
signalling is required for the initial induction of Fgf8 in the
ectoderm by Fgf10 and for the maintenance of Fgf8 expression in the
AER (Barrow et al., 2003;
Galceran et al., 1999).
Tbx5 is expressed throughout the limb bud and is required for the
maintenance of limb outgrowth (Agarwal et
al., 2003; Rallis et al.,
2003).
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