Fig. 8. SHH function in generating the amniote limb skeleton. ozd legs (top) develop with a single, identifiable, Shh-independent skeletal element at each PD level (red), forming a linear series of the anterior-most elements found in wild-type legs (bottom). Therefore, given a functional AER, the limb field contains all the information necessary to form a distally complete limb. In normal development, Shh signaling is differentially required at each PD level to elaborate the formation and patterning of additional limb skeletal elements (blue) along the AP axis. We propose that while the femur (f) is Shh independent, Shh acts in the zeugopod context of the prepatterned tibia (ti) to specify the fibula (fi). In the autopod, Shh acts in the context of the prepatterned d1 to progressively specify the posterior digits (d2, d3, and then d4). We note that Shh is also required to elaborate the posterior fibulare (fl) and basal commune (bc) elements of the tarsus, which respectively fuse to the distal tibia (ti) and proximal metatarsals (mt) by 8.5 days of development (data not shown). tl, tibiale.

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