Figure 8. Model of Gli activity in the schlei mutant.

In the neural tube, a ventral gradient of Shh signaling specifies ventral neuronal cell types, while dorsal Gli3R helps restrict the extent of their domain. In the schlei ventral neural tube, the highest level of Shh responsiveness is lost, but there is an increased range of intermediate-level signaling extending more dorsally, mimicking a shallower, but elongated gradient. Gli3 repressor function is also diminished in schlei, and together, this results in the absence of the highest-level ventral target, the floorplate (FP), combined with a broadened domain competent to form motor neurons (MN) and V2 interneurons. In the limb, a posterior gradient of Shh signaling specifies digit identity while anterior Gli3R restricts digit number. Similar to the neural tube, the Shh gradient appears extended in schlei limbs and together with decreased Gli3R function results in an expansion of Shh target gene expression (Gremlin, Gli1) in the anterior portion of the limb.