UC Irvine

In organisms, tissue development and maintenance must be precisely timed and spatially coordinated to ensure proper form and function. This can be difficult both to develop and to maintain in the complex environments present in organisms, and thus a mechanism that can be finely tuned and regulated must be present. Therefore, when studying the underlying principles of morphogenesis, it is important to consider the crucial biochemical, cellular, and tissue scales simultaneously. This creates a need for a mathematical and computational approach to understanding the complex biology of development. One way of achieving a high level of precision of control is through stem cell lineages. These lineages employ the use of stem cells and their progeny to maintain certain properties necessary for proper tissue function. One such system is found in the stratified inter-follicular epidermis. Here, we develop and use a two dimensional, multi-scale, cell lineage model to explore the molecular, cellular, and physical properties of healthy and diseased epidermis. The model recapitulates a variety of healthy epithelial tissue shapes, including the formation and maintenance of undulating structures, known as rete-ridges. We find that the dermis compliance and the cell-cell adhesion at the dermis-epidermis junction, in conjunction with internal physical pressures due to cell lineage dynamics, play an important role in the tissue morphology. We explore these dynamics to get a better understanding of morphological changes found in diseased skin, including thickening of the tissue and deformation of rete-ridges. Another system in which the molecular mechanisms and cell dynamics driving morphogenesis remains unclear is in diversification of feather vane shapes. Here, we integrate a two dimensional, multi modular mathematical model with transcriptome profiling to elucidate the anisotropic signaling modules which break symmetry, alter cell shape, and generate diverse feather shapes. Overall, this work provides multi-dimensional frameworks to study development and applies them to various biological tissues to better understand their underlying processes.