Specific Aims: The overall goal of this work is to study some of the molecular mechanisms of dedifferentiation and transdifferentiation of muscle-derived tissue that occurs during regeneration in a teleost vertebrate after tail amputation. This is a topic of great importance because stimulation of regeneration in vivo from healthy residual tissues can help replace tissues and organs damaged by injury or disease. S. macrurus is unique among vertebrates in its ability to regenerate its tail including spinal cord, skin, skeleton, muscle, and electric organ following amputation (35,36). Differentiated mesenchymal cells of S. macrurus have the ability to respond to tail amputation by reentry to the cell cycle (36). Our main objective is to use tail regeneration in S. macrurus to begin to identify and study the role of signals that control the transformation of differentiated myogenic cells.
Our specific aims are: (1) to characterize the expression of candidate molecular factors during dedifferentiation following induction of regeneration in vivo, (2) to determine the capacity of blastema cells to induce dedifferentiation of fully mature tissue and, (3) to determine whether the mammalian muscle cells are capable of responding to the signals from the blastemal cells.