Figure 4. Shared developmental histories in fin rays and digits.

In mice (top row), late phase Hox expression (red shaded) marks the distal cells of the limb bud that result in bones of the autopod (wrists and digits). Double knockout of Hoxa13 and Hoxd13 results in the loss of the autopod. In zebrafish wild-type fins (middle row), cells marked by late phase hox expression (red shade) end up in the fin fold and within osteoblasts of the dermal rays. Hoxa13 knockout fish (hoxa13a^-/-, a13b^-/-) and the triple knockout (mosaic for hoxa13b and hoxd13a) have extremely reduced fin rays with increased distal endochondral radials. Note that distal radials are stacked along the proximodistal axis in the posterior of the fins. The results suggest the hypothesis (bottom row) that the knockout phenotype results from a deficit in migration of mesenchymal cells with more cells left in the distal fin bud (increased number of cells in the endochondral disk of mutants fins, Extended Data Fig. 4) and fewer migrating to the fold, thereby resulting in a larger number of endochondral bones and reduced dermal ones. Red shade: late phase Hox expression. Red cells: cells that experienced late phase hox expression. Mouse limbs consist of only endochondral bones, but fish fins contain endochondral (black) and dermal (transparent; fin rays) bones.