Neural tube defects are among the most common human birth disorders. The neural tube forms through rearrangements of epithelial sheets, and apical constriction – the reduction in cell apical surface – is a main driver of neuroepithelial bending. Previous research has implicated a role for calcium homeostasis in apical constriction, but the underlying molecular details of this process remain unclear. Now, Brown and García-García provide genetic evidence that the secretory pathway calcium ATPase (SPCA1), which regulates calcium homeostasis, is required for the apical constriction of neuroepithelial cells in mouse. By characterizing a new Spca1 mutation that leads to exencephaly, they first show that neural tube defects precede apoptosis and therefore cell death is not the primary cause of the malformations, contrary to an earlier study. As Spca1 phenotypes resembled mutants in which apical constriction is defective, the authors further investigated whether Spca1 is required for actomyosin dynamics. They report that the localization of myosin II motors and the actin-binding protein cofilin 1 is perturbed, and that apical F actin and the F-actin/G-actin ratio is decreased upon the loss of SPCA1. Therefore, this study establishes a link between calcium homeostasis and cytoskeletal dynamics in the regulation of neural tube closure in mammals.
