One of the earliest structures in development and precursor to the brain and spinal cord is the neural tube, yet how this key developmental structure forms remains poorly understood. Anteriorly, primary neurulation drives the folding of the flat epithelial sheet into a hollow tube near the head. In the posterior trunk region, secondary neurulation involves the thickening of cells into a cord which subsequently hollows out. Together, these processes form the opposing ends of the hollow neural tube. The convergence of these two mechanisms results in a region of junctional neurulation and notably it is in this junctional region that many neural tube defects (NTD) arise. In researching these NTDs, focus was placed on the planar cell polarity (PCP) pathway, which is crucial for cell and tissue organisation during development and known to play a key role in junctional neurulation. Early research highlighted the Prickle1 protein as particularly significant, with several mutations identified in patients with junctional NTDs. However, we find that loss of Prickle1 does not disrupt the PCP pathway, but instead apical-basal polarity pathways.
Previously, PCP proteins such as Prickle1 have had limited characterisation beyond their roles in the PCP pathway. In my research, I investigate the non-PCP functions of Prickle1 and use this understanding to explore how mutations in Prickle1 contribute to NTDs. I use in vitro biochemical analyses to assess how these mutations affect binding interactions, and quantitative live imaging of transgenic quail models to examine their impact on junctional neurulation in vivo. In doing so, I aim to reveal the effects of key NTD-causing Prickle1 mutations from the protein to the tissue scale.