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1	FGF4 Induced Wnt5a Gradient in the Limb Bud Mediates Mesenchymal Cell Directed Migration and Division Allen, John C 01 December 2013 (has links) (PDF) The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. We demonstrate that Wnt5a does not signal via the Wnt/β-catenin pathway. However, we show that Wnt5a mutants share many common defects with Vangl2 mutants suggesting that Wnt5a signals through the Wnt/planar cell polarity (PCP) pathway. FGF4 AER apical ectodermal ridge Wnt5a Wnt5b Wnt3a limb Ror2 Ror1 Ryk PCP planar cell polarity neural tube vangl2 looptail Cell and Developmental Biology Physiology