Understanding how a homogeneous population of cells organizes into tissues and ultimately forms an embryo is a central challenge in developmental biology. This process requires precise coordination at multiple scales—from the regulation of gene expression in individual cells to the collective forces driving thousands of cells as they shape emerging structures. Although live imaging has illuminated key aspects of these dynamics, post-implantation stages are difficult to study in mouse embryos, and other models often fail to capture crucial features of human morphogenesis. To address this gap, we developed a transgenic quail model that mirrors important early human developmental events and is uniquely suited for real-time imaging of tissue formation.
Using this system, we investigated the formation of the neural tube (NT), which gives rise to the brain and spinal cord. Near the head, the NT forms through primary neurulation but near the tail, the NT forms differently through secondary neurulation. It is critical to nervous system function that these differing morphogenetic processes are reconciled to form a continuous NT in a process recently termed “junctional neurulation”. Most human spinal defects (such as spina bifida) occur in and around the junctional NT, making it a hotspot for morphogenetic defects. By performing quantitative live imaging, we identified two key cellular behaviours—convergence and SNAIL2-dependent epithelial-to-mesenchymal transition (EMT)—that drive NT closure in this junctional region. Whereas convergence is traditionally associated with PCP signalling, mutations in the PCP protein PRICKLE1 (PK1) unexpectedly disrupted cell ingression, revealing a novel PCP-independent role for PK1 in junctional neural tube formation. These findings provide new insights into the mechanisms underlying spinal development and may inform strategies to prevent or mitigate neural tube defects.