ANALYSIS OF GROWTH CONTROL MECHANISMS IN THE ZEBRAFISH

斑马鱼鳍提供了一个理想的模型系统，联合收割机结合遗传，分子和细胞的方法，以揭示机制（S），在脊椎动物的比例增长。斑马鱼在其一生中按比例生长，并保持鳍长和体长之间的恒定比例。已经发现了几种干扰这一过程的突变体，包括短鳍（sof）和长鳍（lof）。个体是sof保持减少鳍长度与身体长度的比例，导致短鳍。 lof突变体在生长过程中没有保持比例性，而是过度生长鳍。 本提案的目标是确定控制斑马鱼成比例生长的机制，以及确定sof如何参与建立成比例生长期间的鳍长。 这将通过三种方法来完成：（1）确定sof和lof突变体的细胞基础，（2）sof基因的鉴定，（3）观察新的sof突变体的鳍生长。 生长控制机制的紊乱导致在人群中鉴定的许多综合征。 这些疾病包括矮树丛综合征、Seckel综合征、过度生长综合征、Beckwith-Wiedemann综合征和Marfan综合征以及癌症。 揭示生长控制的基本机制将导致更好地管理这些和其他生长相关疾病。

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.