FIGURE 5. A positive feedback loop coordinates vertebrate limb development.

From the following article:

Feedback control of intercellular signalling in development

Matthew Freeman

Nature 408, 313-319(16 November 2000)

doi:10.1038/35042500

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The zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER) are the two principal organizing centres of the limb, patterning the anterior/posterior axis and controlling proliferation at the growing tip, respectively. These two essential organizers of development are coordinated in the growing limb tip by a positive feedback loop that makes them mutually dependent. Sonic hedgehog (Shh) from the ZPA activates the expression of fibroblast growth factor (Fgf) in the AER, via a number of signalling components, Formin (Fmn), Gremlin (Gre) and bone morphogenetic protein (BMP); Fgf maintains Shh expression in the ZPA.

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