46. Which one of the following statements regarding limb regeneration in Salamander is correct?
(1) A normal limb is regenerated after amputation, irrespective of whether the cut was made below the elbow or through the humerus.
(2) It occurs by compensatory regeneration and does not include formation of an apical
ectodermal cap.
(3) Regeneration occurs through formation of a blastema, which essentially consists of unspecified multi-potential progenitor cells.
(4) Proliferation of the blastema cells does not require nerves or factors secreted by the nerves.

Key Features of Salamander Limb Regeneration

• Blastema Formation Is Central:
  After amputation, differentiated cells near the wound dedifferentiate to form the blastema. This blastema contains multipotent progenitor cells capable of redifferentiating to regenerate complex limb structures including bone, muscle, cartilage, and connective tissue.

• Dedifferentiation vs. Compensatory Regeneration:
  Unlike compensatory regeneration (which involves proliferation of existing progenitor cells without major dedifferentiation), salamander limb regeneration critically requires blastema formation driven by dedifferentiation.

• Nerve Dependence:
  Successful blastema proliferation depends on factors secreted by nerves. Denervation inhibits blastema growth and regeneration.

• Positional Information:
  Cells in the blastema maintain positional identity, ensuring proper spatial patterning of the regenerating limb.

• Regeneration Is Consistent Across Amputation Levels:
  Regeneration can occur effectively whether the limb is severed below the elbow or through the humerus, with the blastema regenerating the missing segment.

Why Other Statements Are Incorrect

• Regeneration is not solely compensatory and always requires blastema formation, ruling out statement (2).

• Proliferation critically requires nerve signals, invalidating statement (4).

• Statement (1) about regeneration irrespective of cut level is generally true but not as specific or informative as statement (3).

Conclusion

Salamander limb regeneration involves the formation of a blastema consisting mostly of dedifferentiated, multipotent progenitor cells essential for limb restoration. This process is nerve-dependent and distinct from compensatory regeneration, highlighting the remarkable cellular plasticity and molecular control during epimorphic regeneration.

Final Answer:
(3) Regeneration occurs through formation of a blastema, which essentially consists of unspecified multi-potential progenitor cells.