Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum

Abstract

Background Urodele amphibians are capable of regenerating their organs after severe damage. During such regeneration, participating cells are given differentiation instructions by the surrounding cells. Limb regeneration has been investigated as a representative phenomenon of organ regeneration. Cells known as blastema cells are induced after limb amputation. In this process, dermal fibroblasts are dedifferentiated and become undifferentiated similar to limb bud cells. Just like limb bud cells, the induced blastema cells are positioned along the three limb developmental axes: the dorsoventral, the anteroposterior, and the proximodistal. The accurate developmental axes are essential for reforming the structures correctly. Despite the importance of the developmental axes, the relationship between the newly establishing developmental axes and existing limb axes was not well described with molecular markers. Results In this study, we grafted skin from GFP‐transgenic axolotls and traced the cell lineage with position‐specific gene expressions in order to investigate the correlation of the newly established axes and cellular origin. Shh‐ and Lmx1b‐expressing cells emerged from the posterior skin and dorsal skin, respectively, even though the skin was transplanted to an inconsistent position. Shox2, a posterior marker gene, could be activated in cells derived from distal skin. Conclusions Our results suggest that the location memories on anteroposterior and dorsoventral axes are relatively stable in a regenerating blastema though cellular differentiation is reprogrammed.

Variable Shh and Fgf8 positioning in regenerating axolotl limb guarantees consistent limb morphogenesis in different limb sizes

“…Cell origin must have a great influence on limb morphogenesis, even though a developing limb bud and a regenerating blastema exhibit similar genetic cascades in morphogenesis. We have previously demonstrated that the gene expression pattern reflects cell origin 33 . Shh -expressing cells only emerge from posteriorly derived cells.…”

“…However, the ability of the re-expression of Shh or Fgf8 is predetermined by the origin of the cell. Our previous report showed that the spatial location of cells before amputation dictates gene expression in a regeneration blastema 33 . Considering this, the Shh + domain would be restricted within the area that, the posterior-derived cells occupy, under the influence of FGF8.…”

The use of transgenics in the laboratory axolotl

“…Since then, many different studies have used the grafting approach to provide a further detailed understanding of evolution, development, and tissue regeneration in axolotl. 30,[44][45][46][47][48]…”

“…Nevertheless, this study provided important insights on lineage restriction during limb regeneration. Since then, many different studies have used the grafting approach to provide a further detailed understanding of evolution, development, and tissue regeneration in axolotl 30,44‐48 …”

The Use of Larval Sea Stars and Sea Urchins in the Discovery of Shared Mechanisms of Metazoan Whole-Body Regeneration

“…This is not always the case, as the cnidarian Hydra can achieve regeneration with limited contribution from the proliferation of new cells [ 8 ]. Whole-body regeneration also requires the ability of the animal to reset its major body axes through positional cues, such that the correct tissues are regenerated in the correct spatial domain [ 9 , 10 ].…”