Kamal Ghorui
Neural tube defects, such as Spina bifida, are one of the leading congenital disorders (affecting about one in 1,000 live births worldwide) and are associated with the junctional neurulation. Though NTDs are most likely to develop within the first four weeks of pregnancy, it has historically been challenging to observe the specific molecular mechanisms that contribute to their development. A research team at the University of Queensland has utilised sophisticated imaging technologies and transgenic quail embryos to observe, in real time, how the PRICKLE1 protein regulates cellular events during neural tube formation. This new knowledge, obtained by tracking PRICKLE1 activity via junctional NTDs, gives rise to innovative approaches for future clinical diagnosis and preventive treatment.
Understanding the role of PRICKLE1 in human birth defects
PRICKLE1 is an important protein involved in development at the cellular level, especially regarding how tissue structure forms. For many years, it has been studied because of its role in planar cell polarity (PCP) signalling, which allows cells to orient themselves. New research shows this protein has another role, one that’s independent of the PCP pathway, in the process of forming the junctional neural tube. As noted in a thesis of the University of Queensland, PRICKLE1 helps assemble the cortical actomyosin network of midline cells, which is crucial to a process called apical constriction. This provides the driving force for moving cells during epithelial-mesenchymal transition (EMT). Cellular ingression into the neural tube is impaired when there is an interruption in PRICKLE1, which leads to a defect in the structure of the spinal cord.
The role of fluorescent quail embryos in modern research
Quail embryos are ideal models for investigating human neural development because they have a junctional neural tube region that closely resembles human anatomy. Using transgenic quail lines and high-resolution, ‘real-time’ fluorescent imaging, researchers were able to visualise cellular movements that were previously intractable. As noted in a thesis of the University of Queensland, this allowed the researchers to accurately track midline cells as they migrated and ingressed, which provided the first direct evidence of how the disruption of specific proteins causes junctional defects. This approach provides a repeatable and observable system for testing potential translational outcomes, bridging basic developmental biology and human clinical outcomes.
Implications for human health and future screening
Junctional neural tube defects were first formally characterised as a distinct clinical entity in 2017 in medical literature. Unlike more common defects that may be mitigated by folic acid-resistant, junctional defects have lacked effective treatment options. By identifying that PRICKLE1-mediated EMT is the critical driver of these malformations, scientists now have a specific target for research into preventative medicine. These findings may eventually enable clinicians to develop better genetic screening tools and targeted therapies, potentially reducing the incidence of severe birth defects that currently require complex, lifelong surgical intervention.
