ANALYSIS OF GROWTH CONTROL MECHANISMS IN THE ZEBRAFISH

斑马鱼鳍提供了一个理想的模型系统，将遗传学、分子和细胞方法结合起来，揭示脊椎动物比例生长的机制(S)。斑马鱼在一生中按比例生长，并保持鳍长度和身体长度之间的恒定比例。目前已鉴定出几种干扰这一过程的突变体，包括短鳍(Sof)和长鳍(Lof)。体型较弱的个体，鳍长度与体长的比例变小，导致鳍较短。Lof的突变体在生长过程中不保持比例而使鳍长得过长。这项建议的目标是确定控制斑马鱼比例生长的机制(S)，以及确定SOF如何参与确定比例生长过程中的鳍长度。这将通过三种方法来完成：(1)确定sof和lof突变体的细胞学基础，(2)鉴定sof基因，(3)观察新sof突变体的鳍生长。生长控制机制的扰动导致了在人类群体中发现的许多综合症。这些综合症包括林下综合症、塞克尔综合征、过度生长综合征、贝克威德曼综合征和马凡氏综合征，以及癌症。揭示生长控制的基本机制将有助于更好地管理这些疾病和其他与生长相关的疾病。

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.