Regeneration in spiralians: evolutionary patterns and developmental processes.

Animals differ markedly in their ability to regenerate, yet still little is known about how regeneration evolves. In recent years, important advances have been made in our understanding of animal phylogeny and these provide new insights into the phylogenetic distribution of regeneration. The developmental basis of regeneration is also being investigated in an increasing number of groups, allowing commonalities and differences across groups to become evident. Here, we focus on regeneration in the Spiralia, a group that includes several champions of animal regeneration, as well as many groups with more limited abilities. We review the phylogenetic distribution and developmental processes of regeneration in four major spiralian groups: annelids, nemerteans, platyhelminths, and molluscs. Although comparative data are still limited, this review highlights phylogenetic and developmental patterns that are emerging regarding regeneration in spiralians and identifies important avenues for future research.

Restoration of anterior regeneration in a planarian with limited regenerative ability.

Variability of regenerative potential among animals has long perplexed biologists. On the basis of their exceptional regenerative abilities, planarians have become important models for understanding the molecular basis of regeneration. However, planarian species with limited regenerative abilities are also found. Despite the importance of understanding the differences between closely related, regenerating and non-regenerating organisms, few studies have focused on the evolutionary loss of regeneration, and the molecular mechanisms leading to such regenerative loss remain obscure. Here we examine Procotyla fluviatilis, a planarian with restricted ability to replace missing tissues, using next-generation sequencing to define the gene expression programs active in regeneration-permissive and regeneration-deficient tissues. We found that Wnt signalling is aberrantly activated in regeneration-deficient tissues. Notably, downregulation of canonical Wnt signalling in regeneration-deficient regions restores regenerative abilities: blastemas form and new heads regenerate in tissues that normally never regenerate. This work reveals that manipulating a single signalling pathway can reverse the evolutionary loss of regenerative potential.

Acoel and platyhelminth models for stem-cell research.

Acoel and platyhelminth worms are particularly attractive invertebrate models for stem-cell research because their bodies are continually renewed from large pools of somatic stem cells. Several recent studies, including one in BMC Developmental Biology, are beginning to reveal the cellular dynamics and molecular basis of stem-cell function in these animals.

Latent regeneration abilities persist following recent evolutionary loss in asexual annelids.

Regeneration abilities have been repeatedly lost in many animal phyla. However, because regeneration research has focused almost exclusively on highly regenerative taxa or on comparisons between regenerating and nonregenerating taxa that are deeply diverged, virtually nothing is known about how regeneration loss occurs. Here, we show that, following a recent evolutionary loss of regeneration, regenerative abilities can remain latent and still be elicited. Using comparative regeneration experiments and a molecular phylogeny, we show that ancestral head regeneration abilities have been lost three times among naidine annelids, a group of small aquatic worms that typically reproduce asexually by fission. In all three lineages incapable of head regeneration, worms consistently seal the wound but fail to progress to the first stage of tissue replacement. However, despite this coarse-level convergence in regeneration loss, further investigation of two of these lineages reveals marked differences in how much of the regeneration machinery has been abolished. Most notably, in a species representing one of these two lineages, but not in a representative of the other, amputation within a narrow proliferative region that forms during fission can still elicit regeneration of an essentially normal head. Thus, the presence at the wound site of elements characteristic of actively growing tissues, such as activated stem cells or growth factors, may permit blocks to regeneration to be circumvented, allowing latent regeneration abilities to be manifested.

Making heads from tails: development of a reversed anterior-posterior axis during budding in an acoel.

The anterior-posterior axis is a key feature of the bilaterian body plan. Although axis specification during embryogenesis has been studied extensively, virtually nothing is known about how this axis can be established post-embryonically, as occurs in budding animals. We investigated bud formation in the acoel Convolutriloba retrogemma, which reproduces by a remarkable process involving the formation of animals with linked but completely opposite body axes. Reverse axes are established anew during each round of budding and manifestations of the bud's new axis develop gradually, with regionalization of axial patterning genes (Hox and otx) and the establishment of organized musculature occurring secondarily, after bud initiation. A swath of tissue at the parent-bud boundary has no regenerative potential and appears devoid of inherent axial polarity. GSK-3 inhibitor trials suggest that Wnt/beta-catenin or Hedgehog signalling may mediate the establishment of this unpolarized zone. Formation of unpolarized tissue may provide a buffer between opposing polarity cues and be a general mechanism by which budding animals establish and maintain linked body axes. In addition to elucidating the developmental basis of budding in a bilaterian, this study provides insight into convergence in animal budding mechanisms, redeployment of embryonic gene expression during budding, and Hox gene evolution.

Radical modification of the A-P axis and the evolution of asexual reproduction in Convolutriloba acoels.

Acoel worms in the genus Convolutriloba are remarkable in that closely related, morphologically very similar species reproduce asexually by dramatically different processes. Transverse fission, longitudinal fission, and reversed-polarity budding all occur within this genus, indicating an unparalleled ability to alter the A-P axis. Convolutriloba thus offers an exceptional opportunity to investigate the development and evolution of asexual reproduction. Molecular phylogenetic analysis indicates that reversed-polarity budding is ancestral and fission is derived for the genus. A clear difference between budding and fission is indicated by the development of the nervous system, which forms de novo during budding, but regenerates largely by extensions of remaining components of the nervous system during both types of fission. Despite this and other differences between fission and budding, localized muscle disorganization coupled with behaviorally mediated tearing are characteristic of both transverse fission and reversed-polarity budding (though not longitudinal fission), suggesting that a homologous tissue-separation mechanism underlies these two outwardly quite different asexual reproductive modes. We suggest that the ability to split the posterior axis field into two adjacent fields, manifested during both reversed-polarity budding and longitudinal fission, may have been a driving force behind the diversification of asexual reproductive mode in this group.