Nuclei on the move: LINC complex-dependent and -independent mechanisms of nuclear migration in development

Nuclear positioning drives developmental processes from fertilization to neurogenesis. The linker of nucleoskeleton and cytoskeleton (LINC) complex connects nuclei to cytoskeletal force generators that power nuclear migration. Mutations in LINC complex components cause muscular dystrophies and neurodegenerative disorders, yet mechanisms controlling nuclear movement remain poorly understood. We summarize advances from three C. elegans developmental models in different mechanical environments: pronuclear migration across the vast zygotic cytoplasm, hyp7 hypodermal precursor nuclear migration where nuclei span nearly the width of the cell, and P-cell nuclear migration through narrow constrictions. These systems reveal multiple regulatory strategies for nuclear movement. Tissue-specific expression of distinct SUN-KASH combinations determines which cytoskeletal elements engage nuclei. Alternative splicing generates KASH isoforms with opposing motor preferences, and P-cell nuclear migration through constrictions requires four parallel pathways. These findings establish conserved mechanistic principles of nuclear migration, with implications for development, immune cell function, and cancer metastasis.