Search

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function. Although many genes that regulate nuclear movement have been identified, the mechanisms by which these genes act are not known. Using Drosophila melanogaster muscle development as a model system and a combination of live-embryo microscopy and laser ablation of nuclei, we have found that clustered nuclei encompass at least two phenotypes that are caused by distinct mechanisms. Specifically, Ensconsin is necessary for productive force production to drive any movement of nuclei, whereas Bocksbeutel and Klarsicht are necessary to form distinct populations of nuclei that move to different cellular locations. Mechanistically, Ensconsin regulates the number of growing microtubules that are used to move nuclei, whereas Bocksbeutel and Klarsicht regulate interactions between nuclei.

Using Drosophila muscle development as a model system makes possible the identification of genetic pathways, temporal regulation of development, mechanisms of cellular development, and physiological impacts in a single system. Here we describe the basic techniques for the evaluation of the cellular development of muscle in Drosophila in both embryos and in larvae. These techniques are discussed within the context of how the LINC complex contributes to muscle development.

Drosophila is used as a model system to show that the common phenotype of mispositioned nuclei occurs via distinct mechanisms in Emery–Dreifuss muscular dystrophy and centronuclear myopathy., Muscle cells are a syncytium in which the many nuclei are positioned to maximize the distance between adjacent nuclei. Although mispositioned nuclei are correlated with many muscle disorders, it is not known whether this common phenotype is the result of a common mechanism. To answer this question, we disrupted the expression of genes linked to Emery–Dreifuss muscular dystrophy (EDMD) and centronuclear myopathy (CNM) in Drosophila and evaluated the position of the nuclei. We found that the genes linked to EDMD and CNM were each necessary to properly position nuclei. However, the specific phenotypes were different. EDMD-linked genes were necessary for the initial separation of nuclei into distinct clusters, suggesting that these factors relieve interactions between nuclei. CNM-linked genes were necessary to maintain the nuclei within clusters as they moved toward the muscle ends, suggesting that these factors were necessary to maintain interactions between nuclei. Together these data suggest that nuclear position is disrupted by distinct mechanisms in EDMD and CNM.

Cells in vivo exist in a dynamic environment where they experience variable mechanical influences. The precise mechanical environment influences cell-cell interactions, cell-extracellular matrix interactions, and in-turn, cell morphology and cell function. Therefore, the ability of each cell to constantly and rapidly alter their behavior in response to variations in their mechanical environment is essential for cell viability, development, and function. Mechanotransduction, the process by which mechanical force is translated into a biochemical signal to activate downstream cellular responses, is thus crucial to cell function during development and homeostasis. Although much research has focused on how protein complexes at the cell cortex respond to mechanical stress to initiate mechanotransduction, the nucleus has emerged as crucial to the ability of the cell to perceive and respond to changes in its mechanical environment. This additional method for mechanosensing allows for direct transmission of force through the cytoskeleton to the nucleus, which can increase the speed at which a cell changes its transcriptional profile. This review discusses recent work demonstrating the importance of the nucleus in mediating the cellular response to internal and external force, establishing the nucleus as an important mechanosensing organelle.