The tetrapod limb: a hypothesis on its origin.

A wrist joint and structures typical of the hand, such as digits, however, are absent in [Eustenopteron] (Andrews and Westoll, '68, p 240). Great changes must have been undergone during evolution of the ankle joint; the small number of large bones in the fin must somehow have developed into a large number of small bones, and it is very difficult to draw homologies in this region, or even be certain of what is being compared (Andrews and Westoll, '68, p 268). The tetrapod limb is one of the major morphological adaptations that facilitated the transition from an aquatic to a terrestrial lifestyle in vertebrate evolution. We review the paleontological evidence for the fin-limb transition and conclude that the innovation associated with evolution of the tetrapod limb is the zeugopodial-mesopodial transition, i.e., the evolution of the developmental mechanism that differentiates the distal parts of the limb (the autopodium, i.e., hand or foot) from the proximal parts. Based on a review of tetrapod limb and fish fin development, we propose a genetic hypothesis for the origin of the autopodium. In tetrapods the genes Hoxa-11 and Hoxa-13 have locally exclusive expression domains along the proximal-distal axis of the limb bud. The junction between the distal limit of Hoxa-11 expression and of the proximal limit of Hoxa-13 expression is involved in establishing the border between the zeugopodial and autopodial anlagen. In zebrafish, the expression domains of these genes are overlapping and there is no evidence for an autopodial equivalent in the fin skeleton. We propose that the evolution of the derived expression patterns of Hoxa-11 and Hoxa-13 may be causally involved in the origin of the tetrapod limb. Copyright 2001 Wiley-Liss, Inc.