Theoretical and experimental models of hormetic fusion tubulogenesis.

Hormetic morphogens are morphogens such as transforming growth factor beta (TGF-β) in mammals and auxin in plants that induce hormetic responses. For example, in vitro, TGF-β stimulates and inhibits cell proliferation at low and high concentrations respectively. I developed a model of hormetic morphogen gradient control of the morphogenesis of the fusion of bilateral aortic precursors (Anlagen) that form the aorta during development; and validated the model with findings obtained by Daucus Carota fusion experiments. Theoretically, radial concentration gradients of a hormetic morphogen can form hollow (vessels) or solid (Carota) tubular structures. In arteries, blood flow and pressure can shape mural gradients and determine wall curvature and thereby vessel diameter. As Anlagen grow they form a temporary common wall that is subsequently removed, which results in fusion of the Anlagen lumina and an aorta with a lumen diameter that accommodates the combined blood flow to the iliac arteries. Carota seedlings grown close together exhibited proximally fused root cones, serial cross-sections of which exhibited coaxial fusion patterns that closely resembled the predicted vascular fusion patterns, thus validating a role for hormesis and hormetic morphogens in the morphogenesis of the aorta and possibly the morphogenesis of other human midline structures.