O^mUHHI Knockout phenotype | Phase II expression
Figure 6.9 Hox genes and the development of the tetrapod limb. (a) The sequence of growth of a tetrapod limb bud, reading from top to bottom, showing how the stylopod (humerus/femur), zeugopod (forearm/calf) and autopod (hand/foot) differentiate. The pattern is determined by turning on (filled squares) and off (open squares) of Hox genes D-9 to D-13. (b, c) Interpretation of the forelimbs of the osteolepiform fish Eusthenopteron (b) and the tetrapod Acanthostega (c) in terms of development. The developmental axis (solid line) branches radial elements (dashed lines) in a pre-axial (anterior) direction in both forms, and the digits of tetrapods condense in a post-axial direction. (a, based on Shubin et al. 1997; b, c, courtesy of Mike Coates.)
soft tissues in sequence from the body outwards to the tips of the fingers. In an osteolepiform fish (Fig. 6.9b), the developmental axis presumably ran through the main bony elements, and additional bones, radials, developed in front of the axis (pre-axial side). In tetrapods (Fig. 6.9c), the axis in the leg (arm) runs through the femur (humerus), fibula (ulna) and ankle (wrist) and then swings through the distal carpals (tarsals). Radials condense pre-axially at first, as in the osteolepiform, forming the tibia (radius) and various ankle (wrist) bones. The developmental process then switches sides to sprout digits post-axially (behind the axis). This reversal of limb-bud growth direction in the hand/ foot is matched by a reversal of the expression of the Hox genes. In the zeugopod, HoxD-9 is expressed in all five zones, HoxD-10 in the posterior four zones, down to HoxD-13 only in the posterior of the five. In the autopod, on the other hand, HoxA-13 is present in all zones, HoxD-13 in the posterior two zones, and HoxD-10 to HoxD-12 only in the posterior zone.
In Late Devonian tetrapods, six, seven or eight digits were freely produced, and it was only at the beginning of the Carboniferous that tetrapods seem to have fixed on five digits fore and aft. Since then, digital reduction has commonly occurred, down to four (frogs), three (many dinosaurs), two (cows and sheep) or one (horses) fingers and toes. Systematists must beware of interpreting such events as unique, however: the new evo-devo perspective suggests that loss of digits has happened many times in tetrapod evolution, and by the same processes of switching Hox genes on and off.
Read more about Hox genes and limb-bud development at http://www.blackwellpublishing.com/ palaeo/, and about evo-devo topics in general in Carroll (2005) and Shubin (2008).
In early studies of the Hox genes of Dro-sophila, experimenters were amazed to discover that mutations in particular Hox genes might cause the insect to develop a walking leg on its head in place of an antenna. The mutations were not simple changes of the base-pair sequence, but knockouts or deletions of entire functional portions and replacement of their expression domains by more posterior Hox genes. Study of such knockouts showed how each Hox gene worked; in this case the Hox gene acted on the limb bud, the small group of cells on the side of the body that appears early in development and eventually becomes a limb. A particular Hox gene determines how many limb buds there are and where they are located, and other Hox genes determine whether the limb bud becomes a walking leg, a mouthpart or an antenna. If experimenters induce a knockout within a Hox gene, it works its magic in the wrong place, giving the fly extra legs or legs in the wrong place. Mutations of Hox genes in vertebrates normally do not produce these spectacular effects; the embryo often fails and is aborted.
Such mutations need not always result in damage. Duplication of homeobox genes can produce new body segments, and such duplications may have been important in the evolution of arthropods and other segmented animals. The new evo-devo perspective allows us to understand that an arthropod with numerous body segments and 10 or 100 legs may have evolved by a single evolutionary event, perhaps a relatively straightforward mutation of homeobox genes, rather than an elaborate multistep process of gradual addition of segments and legs through many separate evolutionary events. The evo-devo revolution is beginning to explain some of the most mysterious aspects of evolution.
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