Midgut protrusion, rotation, and retraction induced by temporal alteration in differential growth

Herniation, rotation, looping, and retraction of the midgut occur sequentially during midgut morphogenesis. Recent studies have demonstrated the importance of mechanical forces arising from the differential growth between the midgut and mesentery in the formation of small intestinal loops. However, the roles of mechanics and differential growth in the overall process remain unclear. In this study, we developed a computational model of midgut morphogenesis based on continuum mechanics. We showed that the protrusion, rotation, and retraction of the midgut can emerge sequentially because of temporal changes in differential growth. The midgut was modeled as a hyperelastic tube with a Gaussian shape. The differential growth of the midgut and mesentery was modeled by the spatial variation in spontaneous plastic deformation. The hyperelastic tube developed a protrusion by compression-induced deformation, suggesting that other external forces are not necessary for midgut herniation prior to rotation. Appropriate differential growth induced a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mn>90</mml:mn> <mml:mo>∘</mml:mo></mml:msup> </mml:math> rotation of the tube. A less-growing mesentery attempts to face inward to minimize the tensile forces, which causes tube twisting and results in midgut rotation. Excess differential growth may cause the retraction of the midgut before the formation of small intestinal loops. The results of this study will serve as reference in future studies on embryology and tissue engineering.