Dynamics and ultrastructure of myoblast fusion and the involvement of the APC/CFzr

所有高等生物体的肌肉都是在胚胎发生过程中通过单个成肌细胞协调融合成较大的合胞体肌纤维而产生的。在脊椎动物中，成千上万的单个成肌细胞有助于形成一个单独的肌肉。在对胚胎中影响心脏和肌肉发育的突变进行遗传筛查期间，我们将APC/CFzr确定为成肌细胞融合过程中的一个新的关键参与者。fzr突变的胚胎表现出成肌细胞融合的停滞，并在胚胎发生结束时表现出成熟肌纤维的大量减少以及未融合的成肌细胞的进入。在这个提议中，我们的目标是通过应用最先进的光学和电子显微镜以及蛋白质组学方法来识别和理解APC/CFzr对融合过程的机制。

Somatic muscles of all higher organisms arise during embryogenesis by the coordinated fusion of individual myoblasts into larger, syncytial muscle fibres. In vertebrates, thousands of single myoblasts contribute to the formation of one individual muscle. During a genetic screen for mutations affecting heart and muscle development in the embryo, we identified the APC/CFzr as a novel key player during myoblast fusion. Embryos mutant for fzr exhibit an arrest of myoblast fusion, and display a massive reduction of mature muscle fibres as well as an access of unfused myoblasts by the end of embryogenesis. In this proposal, we aim to identify and understand the mechanism of the APC/CFzr on the fusion process by applying state-of-the art light- and electron microscopy as well as proteomic approaches.