Neurotrophic influence on proliferation-differentiation decisions during amphibian forelimb regeneration: an hypothesis

Amphibian forelimb regeneration is under neural influence. Although the precise role of nerves is unknown, clear influence on macromolecular synthesis and on mitosis have been demonstrated. The hypothesis presented here proposes that neural input is directed primarily at influencing the decision of blastemal cells either to proliferate or to prepare to express differentiated phenotypes. This is considered to be accomplished by an interplay between the catecholamine neurotransmitters and neurotrophic peptides using cyclic nucleotides (cAMP) and Ca2+, respectively, as intracellular mediators. This coordination of proliferation-differentiation decisions in regenerating limbs is proposed to be primarily, but not exclusively, the function of nerves.