Embryonic morphogenesis of a complex organism requires proper regulation of patterning and directional growth. Planar cell polarity (PCP) signaling is emerging as a crucial evolutionarily conserved mechanism whereby directional information is conveyed. PCP is thought to be established by global cues, and recent studies have revealed an instructive role of a Wnt signaling gradient in epithelial tissues of both invertebrates and vertebrates. However, it remains unclear whether Wnt/PCP signaling is regulated in a coordinated manner with embryonic patterning during morphogenesis. Here, in mouse developing limbs, we find that apical ectoderm ridge-derived Fgfs required for limb patterning regulate PCP along the proximaldistal axis in a Wnt5a-dependent manner. We demonstrate with genetic evidence that the Wnt5a gradient acts as a global cue that is instructive in establishing PCP in the limb mesenchyme, and that Wnt5a also plays a permissive role to allow Fgf signaling to orient PCP. Our results indicate that limb morphogenesis is regulated by coordination of directional growth and patterning through integration of Wnt5a and Fgf signaling.
[1]Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Pokfulam, Hong Kong, Peoples R China.
[2]NHGRI, Dev Genet Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[3]NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[4]Jilin Univ, China Japan Union Hosp, Dept Hand Surg, Changchun 130033, Jilin, Peoples R China.
[5]Harvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA.
[6]Natl Inst Genet, 1111 Yata, Mishima, Shizuoka 4118540, Japan.
[7]Zhejiang Univ, Life Sci Inst, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China.
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