X-Nico

Limb bud

This FGF10 expression stimulates WNT3 expression in the above ectodermal cells – resulting in formation of the apical ectodermal ridge (AER) as well as inducing FGF8 expression.

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Before limb development begins, FGF10 expression becomes restricted to the proliferating mesenchymal cells of the lateral plate mesoderm, which form the limb bud and become limb mesenchyme.

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Also induces the mesenchymal cells to secrete FGF10, which acts through WNT3A to sustain the AER’s expression of FGF8.

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WNT2B and WNT8C stabilize this FGF10 expression in the forelimb and hindlimb, respectively.

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FGF10 = Initially, Tbx proteins induce secretion of FGF10 by cells in the lateral plate mesoderm.

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#When Shh normally secreted from the ZPA is inhibited (either through use of tamoxifen or Shh-null mutants) the AER morphology, particularly its anterior extent, is perturbed and its FGF8 signaling decreased.

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#Placement of FGF10-containing beads beneath chick ectodermal cells results in the formation a limb bud, AER, ZPA and, subsequently, an entire limb.

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Later, FGF10 expression is restricted to the developing limb mesenchyme, where it is stabilized by WNT8C or WNT2B.

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#Knocking out Tbx4 or Tbx5 knockout prevents FGF10 expression in the lateral plate mesoderm in mice.The Hox pathway may affect Tbx expression, which in turn affects FGF10 expression.

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WNT3A = Acts as a middle man in the positive feedback loop between the AER and limb mesenchyme.