| Description |
According to the National Center for Medical Rehabilitation Research, each year in the United States more than 100,000 individuals lose a limb due to traumatic injury or disease; 7,800 are paralyzed due to spinal cord injury. It is conceivable that these conditions could be treated by activating the body's own genetic instructions to reproduce missing structures or organs. A few vertebrate animals, including urodele amphibians and teleost fish, have an exceptional ability to regenerate various structures, such as limbs, spinal cord, and optic nerve. Limb regeneration in urodeles and fin regeneration in teleosts both appear to include the stages of wound healing and establishment of wound epithelium, recruitment of the blastema, which is defined as a mass of pluripotent mesenchyme cells, and differentiation and outgrowth of the regenerate. Here molecular biological and genetic approaches were applied to study cellular and molecular mechanisms of zebrafish fin regeneration. A classical genetic approach was used to identify four mutants defective in fin regeneration. Histological and molecular analysis shows that these mutants blocked during various stages of fin regeneration. One of these mutations, emmental (emm), prevents formation of a functional blastema through defective cell proliferation and increased apoptosis. Positional cloning revealed that mutation of a zebrafish homologue of yeast sly1 causes the emm phenotype. sly1 is upregulated in blastemal cells during blastema formation and regenerative outgrowth. The data indicate that sly1 is essential for enhanced proliferation that occurs in blastema during regeneration. Another mutant, nightcap (ncp), is specifically blocked during regenerative outgrowth. Positional cloning revealed that <italic>ncp |
