Neural tube defects (NTDs), including spina bifida, are among the most common birth defects in humans. Although the incidence of NTDs has been dramatically reduced by dietary supplementation with folic acid, not all NTDs are folate responsive, and the mechanisms underlying failure in neural tube closure are still incompletely understood. Now, Lee Niswander and colleagues show that the transmembrane protein TMEM132A regulates neural tube closure in mice in a folate-independent manner: Tmem132a mutants display a caudal NTD. Tissue patterning appears to be unaffected, but migration of the underlying paraxial mesoderm appears to be disrupted. Recent theoretical work has suggested that neural tube closure could be driven by migration of the underlying mesoderm; the Tmem132a mutant phenotype provides experimental support for this model. In cell culture assays, knockdown of Tmem132a leads to changes in cell morphology, with migrating mutant cells displaying fewer lamellpodia and more filopodia, to decreased expression of integrin ?1 and to reduced activation of integrin pathway signalling factors. Although the mechanism by which TMEM132A regulates integrin expression has yet to be uncovered, these findings demonstrate a crucial role for this transmembrane protein in regulating mesoderm migration and hence neural tube closure.