The mutant axolotl Short toes exhibits impaired limb regeneration and abnormal basement membrane formation.

Abstract

The mutant axolotl Short toes develops with abnormal kidneys, Mullerian ducts, and limbs and provides one of the few experimental systems for developmental studies in amphibia. The present paper describes another deviation from this animal's normal physiology, which is very characteristic of the wild type: amputated limbs of Short toes fail to regenerate. A blastema is formed but differentiation does not occur. Detailed histological analysis provides evidence of abnormal formation of the basement membrane and accumulation of extracellular matrix within the blastema, which could be attributed to an imbalance of extracellular matrix and basement membrane proteins. The basement membrane develops much thicker and is convoluted in the arrested blastema of mutant animals. In contrast to the limbs, the tails of Short toes regenerated normally with no apparent abnormalities. No gross genomic aberrations have been detected between normal and mutant DNA, indicating that a large deletion or insertion is not likely to be the cause of this mutation.

Probability of regenerating a normal limb after bite injury in the Mexican axolotl (Ambystoma mexicanum)

“…Conversely, limbs arising from abnormal development would not be expected to have appropriately patterned tissues to orchestrate regeneration, as is the case for the short‐toes mutant (Del Rio‐Tsonis et al. ). We amputated the limbs of eight axolotls: (1) three axolotls were missing almost the entire limb and only presented a small (∼3 mm) amount of upper arm tissue; (2) three axolotls were missing the hand or toes on the forelimb; (3) one axolotl presented a deformed wrist and hand; and (4) one axolotl presented fused digits on a hind limb.…”

Matrix metalloproteinase expression and function during fin regeneration in zebrafish: Analysis of MT1-MMP, MMP2 and TIMP2

“…Previous studies in amphibian limb regeneration indicate that basal lamina component synthesis (e.g. laminin, type IV collagen) is generally associated with the wound epithelium (Del Rio-Tsonis et al, 1992), while interstitial matrix component synthesis (e.g. collagen XII, fibronection, tenascin, hyaluronan) can be associated with both the blastema and wound epithelium (Tassava, 1993;Onda et al, 1991).…”

Matrix metalloproteinase expression during blastema formation in regeneration‐competent versus regeneration‐deficient amphibian limbs

“…The s/s blastema has an overabundance of ECM, and develops a convoluted basal lamina under the wound epidermis that prevents normal epidermal-mesenchymal interactions. The s/s limb muscle has a reduced number of satellite cells, which apparently do not contribute to the blastema (Del Rio- Tsonis et al, 1992;Tsonis et al, 1993;Sato and Chernoff, 2007). The Xenopus froglet limb forms a pseudoblastema of fibroblasts (fibroblastema) that grows and differentiates into a symmetrical spike consisting of cartilage and loose connective tissue lacking muscle (Korneluk and Liversage, 1984).…”