Why is limb regeneration possible in amphibians but not in reptiles, birds, and mammals?

Abstract

The capacity to regenerate limbs is very high in amphibians and practically absent in other tetrapods despite the similarities in developmental pathways and ultimate morphology of tetrapod limbs. We propose that limb regeneration is only possible when the limb develops as a semiautonomous module and is not involved in interactions with transient structures. This hypothesis is based on the following two assumptions: To an important extent, limb development uses the same developmental mechanisms as normal limb development and developmental mechanisms that require interactions with transient structures cannot be recapitulated later. In amniotes limb development is early, shortly after neurulation, and requires inductive interactions with transient structures such as somites. In amphibians limb development is delayed relative to amniotes and has become decoupled from interactions with somites and other transient structures that are no longer present at this stage. The limb develops as a semi-independent module. A comparison of the autonomy and timing of limb development in different vertebrate taxa supports our hypothesis and its assumptions. The data suggest a good correlation between self-organizing and regenerative capacity. Furthermore, they suggest that whatever barriers amphibians overcame in the evolution of metamorphosis, they are the same barriers that need to be overcome to make limb regeneration possible in other taxa.

Salamander limb development: Integrating genes, morphology, and fossils

“…They proposed that although much of the development of the limb is similar in all tetrapods, the limbs of amphibians develop as a semiautonomous unit, while in amniotes, limb development primarily takes place in the phylotypic stage in which many parts of the embryo are patterned and a strong interaction between secondary fields and transient structures like the limb bud, somites, notochord, and neural tube takes place. The limb buds occur at comparable stages in all investigated developmental series of amniotes, in which the organization of the embryo is still strongly dependent on interactions between different embryonic units (Galis and Metz, 2001;Galis et al, 2003b). Under this hypothesis, a number of transient structures, which are only present in the early embryo, are necessary for limb development and these interactions cannot be repeated at a later stage, because the structures necessary for induction and interaction of limb structures have disappeared or differentiated (Galis et al, 2003b).…”

“…The limb buds occur at comparable stages in all investigated developmental series of amniotes, in which the organization of the embryo is still strongly dependent on interactions between different embryonic units (Galis and Metz, 2001;Galis et al, 2003b). Under this hypothesis, a number of transient structures, which are only present in the early embryo, are necessary for limb development and these interactions cannot be repeated at a later stage, because the structures necessary for induction and interaction of limb structures have disappeared or differentiated (Galis et al, 2003b).…”

“…Beyond the transition into the nerve-dependent state of the blastema, the events following in the regeneration process (including the expression of Hoxd-11 and Shh) are basically recapitulating developmental processes (Gardiner et al, 1999). Furthermore, the limb patterning processes are also similar in developing and regenerating limbs in terms of their signaling centers: the epidermis forms an AER equivalent zone in developing limbs and the wound epidermis plays an important role in the induction of the blastema; a Shh-expressing region with polarizing influence (ZPA) is present in both the limb bud and the blastema; there is a proliferation zone in the developing limb bud and in the mesenchymal cone of the blastema (Goss, 1969;Torok et al, 1999a;Galis et al, 2003b). Finally, the limb bud and the regeneration blastema both have a high degree of self-organization capacity and can be successfully transplanted and explanted to other body regions of the same animal or other individuals (Galis et al, 2003b).…”

Paedomorphic Ossification in Porpoises with an Emphasis on the Vaquita (<I>Phocoena sinus</I>)

“…Moreover, one of the best studied systems of evolutionary and developmental biology is the tetrapod limb. Heterochrony, or a change in the timing of developmental processes (Smith, 2003), during early limb development and chondrogenesis of tetrapods has led to a wealth of morphological variation: for instance, the precocial development of forelimbs of marsupials (Smith, 2003;BinindaEmonds et al, 2007), the regenerative abilities of amphibian limbs (Galis et al, 2003), the precocial hindlimb development of frogs (Schlosser, 2001;Bininda-Emonds et al, 2007), the elongated digits of bats (Sears et al, 2006), and the supernumary phalanges in the digits of dolphins (Richardson & Oelschläger, 2002). This study investigates the role of heterochrony in shaping the limb of the porpoise.…”

Segmental pattern formation following amputation in the flagellum of the second antennae ofAsellus aquaticus(Crustacea, Isopoda)

“…Goss 1992;, 2003, 2004Brockes et al 2001;Galis et al 2003;Brockes & Kumar 2005;Sánchez Alvarado & Tsonis 2006). Many arthropods regenerate their appendages easily (reviewed in Maruzzo et al 2005); however, these animals have not been adequately explored as experimental models in this regard.…”