King's College London

This study reveals that vascular invasion into the dental epithelium is a critical step in the development of ameloblasts, the cells responsible for enamel formation. Using mouse and human tooth models, the researchers discovered:

• Endothelial cells invade the outer enamel epithelium (OEE) during the bell stage of tooth development, migrating through the stellate reticulum to reach the ameloblast layer.

• This process is driven by dynamic VEGF (vascular endothelial growth factor) signaling, which shifts from the OEE to the ameloblast layer as development progresses.

• Hedgehog signaling is essential for enabling this invasion. Mice lacking epithelial Hedgehog signaling (K14creSmoothenedfl/fl mutants) showed failure of vascular migration through the OEE leading to disruption of the epithelial tissues.

• Similarly, mice with endothelial cells unable to respond to VEGF (Cdh5creERT2 Vegfr2fl/fl mutants) also exhibited failed vascular migration leading to defective ameloblast differentiation and cell death.

• The invasion involves basement membrane breakdown, reduced tight junctions, and localized apoptosis in the OEE, facilitating endothelial cell entry.

 

Why This Is Significant

• Challenges previous assumptions: Traditional views held that vasculature did not penetrate the enamel organ. This study shows direct invasion is necessary for enamel cell development.
• Highlights critical signaling pathways: Understanding the roles of VEGF and Hedgehog signaling in tooth vascularization opens new avenues for regenerative dental therapies, such as directing vascularization of bioengineered dental tissues.
• Conserved mechanism across species: The findings in both mouse and human models suggest a fundamental biological process in mammalian tooth development.

Find out more and read the paper here: https://journals.sagepub.com/doi/full/10.1177/00220345251341850