Neural tube closure occurs through highly orchestrated cell shape changes mediated by actin dynamics. Its failure results in some of the most common and severe human congenital malformations. Cofilin 1, an actin-depolymerising protein, is known to be involved in neural tube closure but its precise functions had not been elucidated. In this study (p. ), Joaquim Grego-Bessa and colleagues show that the absence of cofilin 1 in mouse leads to defective neural tube closure, reduced cell number, altered cell shape and cell cycle kinetics. The protein is enriched at both apical and basal domains of the neuroepithelium but, intriguingly, has opposing activities on either side of the cell. Apically, although localisation of the apical polarity complexes remains unchanged, phosphorylation of myosin light chain is impaired in cofilin 1 mutants. By contrast, basally, the absence of cofilin 1 leads to an accumulation of actin and phosphorylated myosin light chain, ectopic tight junction-like structures and disruption of the basement membrane and hence of epithelial organisation. Altogether, these results shed light on the cellular mechanisms of neural tube closure and reveal a dual role for cofilin that is presumably dependent on the intracellular context.
