ANALYSIS OF GROWTH CONTROL MECHANISMS IN THE ZEBRAFISH

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The zebrafish fin offers an ideal model system to combine genetic, molecular, and cellular methods to reveal the mechanism(s) which govern proportionate growth in vertebrates. Zebrafish grow proportionately throughout their lives, and maintain a constant ratio between fin length and body length. Several mutants which disturb this process have already been identified, including short fin (sof) and long fin(lof). Individuals that are sof maintain a diminished fin length to body length ratio, resulting in short fins. Mutants for lof overgrow the fins without maintaining proportionality during growth. The goals of this proposal are to determine the mechanism(s) controlling proportionate growth in zebrafish, as well as to determine how sof is involved in establishing fin length during proportionate growth. This will be accomplished using three approaches: (1) determining the cellular basis for sof and lof mutants, (2) the identification of the sof gene, and (3) observing fin growth in new sof mutants. Perturbations of growth control mechanisms results in numerous syndromes identified in the human population. These include the undergrowth syndrome, Seckel syndrome, the overgrowth syndromes, Beckwith-Wiedemann syndrome and Marfan's syndrome, and cancer. Revealing the basic mechanisms of growth control will lead to better management of these and other growth-related diseases.