Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development the size of individual muscle fibers must dramatically enlarge to match with skeletal growth. How muscle growth is coordinated with growth of the contractile apparatus is not understood. Here, we use the large Drosophila flight muscles to mechanistically decipher how muscle fiber growth is controlled. We find that regulated activity of core members of the Hippo pathway is required to support flight muscle growth. Interestingly, we identify Dlg5 and Slmap as regulators of the STRIPAK phosphatase, which negatively regulates Hippo to enable post-mitotic muscle growth. Mechanistically, we show that the Hippo pathway controls timing and levels of sarcomeric gene expression during development and thus regulates the key components that physically mediate muscle growth. Since Dlg5, STRIPAK and the Hippo pathway are conserved a similar mechanism may contribute to muscle or cardiomyocyte growth in humans.

中文翻译：

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河马途径通过调节肌节基因表达来控制肌原纤维的组装和肌纤维的生长

骨骼肌由巨大的细胞（称为肌纤维）组成，内含产生力的肌原纤维。在发育过程中，单个肌肉纤维的大小必须显着增大以与骨骼生长相匹配。肌肉生长与收缩装置的生长如何协调尚不清楚。在这里，我们使用大型果蝇飞行肌肉以机械方式解释如何控制肌肉纤维的生长。我们发现，河马通路核心成员的调节活性是支持飞行肌肉生长所必需的。有趣的是，我们将Dlg5和Slmap识别为STRIPAK磷酸酶的调节剂，该酶对Hippo产生负调节作用，从而使有丝分裂后的肌肉得以生长。从机理上讲，我们表明，河马途径控制发育过程中肌节基因表达的时机和水平，从而调节物理上介导肌肉生长的关键成分。由于Dlg5，STRIPAK和Hippo途径被保守，类似的机制可能有助于人类的肌肉或心肌细胞生长。