During polarized cell migration, the nucleus becomes positioned away from the leading edge in mechanism that is dependent on actin retrograde flow. Nuclear movement is regulated by Cdc42, a small RhoGTPase, and its effector MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase). MRCK phosphorylates and activates myosin II, resulting in nuclear movement away from the leading edge. This work suggests that the nucleus is moved by actin cytoskeleton (cf opposite figure)(Gomes et al. 2005).

 

In mature myofibers, nuclei are positioned at the periphery of the cell with some nuclei clustered at the neuromuscular synapse. However, in immature myofibers, the nuclei accumulate at the cell center. Based on these observations, at least three nuclear movements or positioning events are predicted to occur during muscle fiber formation :

We want to identify the mechanisms and the molecular pathways that regulate these different nuclear movement and position events.  We will then be able to study the role of nuclear positioning during myofiber formation and function.