A CDC-42-regulated actin network contributes to nuclear migration through constricted spaces in C. elegans.

Successful nuclear migration through constricted spaces between cells or in the extracellular matrix relies on the ability of the nucleus to deform. Little is known of how this takes place in vivo. We study confined nuclear migration in Caenorhabditis elegans larval P-cells, which is mediated by the LINC complex to pull nuclei towards the minus ends of microtubules. Null mutations of LINC component unc-84 lead to a temperature-dependent phenotype, suggesting a parallel pathway for P-cell nuclear migration. A forward genetic screen for enhancers of unc-84 identified cgef-1 (CDC-42 Guanine Nucleotide Exchange Factor). Knockdown of CDC-42 in the absence of the LINC complex led to a P-cell nuclear migration defect. Expression of constitutively active CDC-42 partially rescued nuclear migration in cgef-1; unc-84 double mutants suggesting CDC-42 functions downstream of CGEF-1. The Arp2/3 complex and non-muscle myosin II (NMY-2) were also found to function parallel to the LINC pathway. In our model, CGEF-1 activates CDC-42, induces actin polymerization through the Arp2/3 complex to deform the nucleus during nuclear migration while NMY-2 helps push the nucleus through confined spaces.