Subcellular Mechanochemical Model to Study Growth Regulation

Growth regulation is an important question in developmental biology and remains unclear for many living systems. Abnormal development and fatal diseases, such as cancer, can be result of uncontrolled tissue growth. The Drosophila wing disc, an epithelial primordial organ that later forms the adult fruit fly wing, is appropriate to study growth regulation because of its relatively simple geometry, limited number of cells, rapid growth, and a well understood molecular signaling network. Nevertheless, the mechanism of growth regulation in Drosophila wing disc tissue remains a subject of intense debate. Multiple mechanisms for growth regulation have been proposed, following the substantial evidence that suggests morphogens regulate growth. However, most existing models focus on either the biochemical signaling pathway or mechanical properties. Very few attempt to incorporate both factors in a mechanistic way. Here we developed a coupled mechanochemical model at sub-cellular level to study growth regulation controlled by the morphogen gradient with cell mechanics taken into account to achieve spatial homogeneous growth and the asymmetric shape of the tissue. The model suggested the shape of the morphogen gradient affected the tissue growth rate and final shape. Moreover, the feedback regulation on the morphogen facilitated the tissue growth through shaping the gradient.