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Fig. 7. A model of AER function in development of the mouse forelimb
autopod. (A,B) AER maintenance is essential for AER-FGF
signaling and generation of autopod progenitors. Schematic diagrams of early
limb buds in transverse views (top row in A,B) and whole-mount dorsal views
(bottom row in A,B) to illustrate development of the AER (green) and autopod
progenitors, as marked by Hoxa13 expression (red). Red dots indicate
dying cells in the ventral ectoderm and AER. (A) In control forelimb buds, the
AER is maintained and AER-FGF production (orange) is normal. As a result, FGF
signaling in the distal limb bud mesenchyme (LBM) is sustained and autopod
progenitors are generated at the 31-32 s stage. The progenitor pool expands
subsequently and a sufficient number of skeletal progenitors are available to
form a normal autopod when condensation starts at around the 46 s stage. (B)
In Fgfr2AER-KO forelimb buds, the AER is not maintained
because of increased cell death and AER-FGF production progressively
decreases. As a result, FGF signaling in the distal mesenchyme is reduced and
generation of autopod progenitors is delayed by 2-somite stages until the
33-34 s stage. Although the progenitor pool expands grossly normally at later
stages, it fails to produce a sufficient number of skeletal progenitors to
form a normal autopod at the onset of autopod condensation.