Migration of cells through constricted spaces occurs throughout development as cells traverse tissues and the extracellular matrix to reach their final destination. A limiting factor here is the rate of nuclear migration; compared with the cell body, the nucleus is more rigid and its deformability must be regulated to permit nuclear migration without damaging its membrane. Although extensively studied in vitro, our understanding of nuclear migration in vivo is limited. In this study, Daniel Starr and colleagues develop an in vivo model to study nuclear migration of larval hypodermal precursor (P cells) in C. elegans, which migrate and squeeze through a ∼200 nm space between the body wall muscles and cuticle during development. The authors perform a forward genetic screen for enhancers of unc-84, a component of the LINC complex, which is known to regulate nuclear migration. Here, they identify CGEF-1, a guanine nucleotide exchange factor for the Rho GTPase CDC-42. Indeed, the authors show that CGEF-1 activates CDC-42 during P-cell nuclear migration. Further, knockdown of downstream effectors, such as the Arp2/3 complex, which modulates the actin cytoskeleton, and non-muscle myosin II (NMY-2), needed for actomyosin contractions, results in nuclear migration defects. Thus, the authors propose that CGEF-1, via modulation of cytoskeletal dynamics, aids in nuclear deformation during P-cell nuclear migration in vivo.