Fig. 8. A model of signaling crosstalks regulating GT development. Evidence indicates that canonical WNT acts upstream of Fgf8 and Shh in the dUE. Fgf8 expression in turn is required for establishing distal mesenchymal gene expression in the GT. Shh expression is also dependent on WNT activity. Shh normally represses Bmp4 expression in the dUE. When WNT is constitutively activated, Bmp4 is ectopically turned on in dUE. The coordinated regulation of positive (e.g. Fgf8 and Shh, green) and negative (e.g. Bmp4, red) regulators of GT outgrowth is essential to maintain the homeostasis of the UE, as well as normal patterning of the GT. The pink region represents the distal mesenchyme; the green region represents the UE.