Discovering the unexpected: Insights into the dynamics of mouse neural tube closure revealed by time-lapse imaging

The use of time-lapse imaging to study neural tube closure in mouse embryos has provided unexpected insights into the complex morphogenetic processes involved. When neural tube closure is disrupted, it leads to neural tube defects (NTDs), which are among the most common structural birth defects in humans, associated with long-term disabilities and death. This review explores the growing body of research on time-lapse imaging experiments conducted in mice, emphasizing discoveries of the dynamic cellular movements and changes that enable neural tube formation. Advances in mouse embryo culture and live imaging techniques have enabled visualization of dynamic cellular movements and shape changes during neural tube formation, allowing researchers to observe abnormal cell behaviors in genetic mouse models with neural tube closure defects. These studies use transgenic reporters, conditional mouse genetics, and various physical and pharmacological interventions to track tissue and cell behavior and elucidate the underlying molecular and biophysical mechanisms as neural folds rise and fuse at the dorsal midline. Observing neural tube closure in real time has led to important findings, including revealing the crucial role of the surface ectoderm in supporting neural fold elevation and fusion. The coordination of apical constriction with cell cycle progression and apoptosis helps shape the neural plate. Analyzing convergent extension shows that oriented neighbor exchanges-requiring planar cell polarity signaling-drive polarized protrusive activity and actomyosin contractility, along with coordinated apical constriction to elevate and bring the neural folds together. Future innovations are expected to improve the measurement of biomechanical forces during neural tube formation and visualization of deep tissues to clarify mechanisms of cranial mesenchyme morphogenesis during cranial neural fold elevation.