A dynamic Hedgehog gradient orients tracheal cartilage rings

SUMMARY The patterning of periodic stripes during embryonic development generates similar structures that repeat at regular spatial intervals within a tissue. These patterns are often attributed to a Turing-like mechanism, which self-organizes characteristically spaced stripes, but these patterns are predicted to be disorganized. Conversely, well-oriented, parallel stripes are often observed in nature. We investigate this phenomenon during the formation of the cartilage rings that support the amniote airway. We find evidence that a Turing-like mechanism underpins the formation of the repeating cartilage elements. Additionally, SHH is transiently expressed in a thin dorsal domain along the length of the developing trachea, resulting in a dorsoventral gradient of Hedgehog activity that recedes over time. Using mathematical modelling, we predict that the spatiotemporal dynamics of the gradient are required to organize the stripes into parallel rings. Comparing in silico predictions with experimental SHH manipulations shows that the Hedgehog gradient is essential for proper tracheal cartilage patterning.