Root nodulation in plants is a form of de novo organogenesis and involves the dedifferentiation of root cortical cells in response to rhizobia-derived factors. However, due to the complexity of this event, our understanding of the factors and mechanisms that initiate nodule formation is limited. Now, Takuya Suzaki and co-workers (p. 2441) reveal a role for endoreduplication during the onset of nodule development in Lotus japonicus. The researchers identify novel nodulation-deficient mutants that harbour mutations in VAG1, which encodes a protein that is orthologous to a component of the Arabidopsis topoisomerase VI complex that has been implicated as a regulator of endoreduplication. In line with this, the authors report that the number of endoreduplicated cells in vag1 mutant nodules is reduced compared with that of controls. Importantly, the analysis of nuclear size suggests that VAG1-mediated endoreduplication is crucial for the initiation of nodule formation. Finally, the researchers demonstrate that infection threads, the specialized structures used by rhizobia to invade host cortical cells, elongate towards endoreduplicated cells, and this directional elongation is perturbed in vag1 mutants. These findings highlight an essential role for endoreduplication during root nodule development and suggest that VAG1-mediated endoreduplication is required for the efficient guidance of symbiotic bacteria to host cells.