Fibroblast growth factors induce additional limb development from the flank of chick embryos

Abstract

Fibroblast growth factors (FGFs) act as signals in the developing limb and can maintain proliferation of limb bud mesenchyme cells. Remarkably, beads soaked in FGF-1, FGF-2, or FGF-4 and placed in the presumptive flank of chick embryos induce formation of ectopic limb buds, which can develop into complete limbs. The entire flank can produce additional limbs, but generally wings are formed anteriorly and legs posteriorly. FGF application activates Sonic hedgehog in cells with polarizing potential to make a discrete polarizing region. Hoxd-13 is also expressed in the ectopic bud, and an apical ectodermal ridge forms. A limb bud is thus established that can generate the appropriate signals to develop into a complete limb. The additional limbs have reversed polarity. This can be explained by the distribution of cells in the flank with potential polarizing activity. The results suggest that local production of an FGF may initiate limb development.

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

“…Alternatively, the localization of the ZPA may depend on a mechanism similar to the localization of the limbs themselves. We know now that limb initiation depends on the local production of Fgfs in the lateral plate mesoderm (Cohn et al, 1995;reviewed in Ohuchi and Noji, 1999). This finding is likely triggered by a signal coming from the paraxial mesoderm, as proposed initially by Madeleine Kieny (Kieny, 1969) as well as Madeleine Pinot (Pinot, 1970) and reinvestigated by Trent Stephens (Stephens et al, 1991).…”

The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP‐mediated cell death

“…Reciprocally, the drastic reduction in FGF signaling from the AER produced by the simultaneous removal of Fgf8 and Fgf4, the two FGFs with the strongest expression in the AER, results in the failure to form a limb (Sun et al, 2002;Boulet et al, 2004). FGFs can even trigger the whole cascade of events that leads to the development of a supernumerary limb when applied to a responding tissue such as the flank (Cohn et al, 1995;Isaac et al, 2000).…”

Fin development in a cartilaginous fish and the origin of vertebrate limbs

“…Balinsky first discovered this in newts 15 but limb-forming potential has now been described in both chick and mouse embryos 16,17 . This remarkable property is associated with the potential of flank cells to form a polarizing region 17 .…”