The tube sizes of the internal organs are various. Some of these show large lumens that require long developmental period through the several embryonic stages, yet its developmental processes are still poorly understood. The trachea is a large tubular structure, which is part of the respiratory system, and the internal diameter of the trachea influences the efficiency of respiration. Malformations of the trachea, such as tracheostenosis, are known to affect respiratory ability in the postnatal period; however, the developmental process of the trachea is still not well understood. In this project, we will challenge to analyze tracheal development by three-dimensional and quantitative methods. Especially we will focus on single cell behaviors and the integration of single cells over long-term development.

We will investigate expansion processes of the tracheal lumen in the middle to late developmental stage. In particular, we will deeply analyze epithelial remodeling process in which fetal epithelial cells are rearranged into pseudostratified tissue by acquiring uniformed apical surface and columnar cell shape. We will dissect epithelial contributions to the luminal expansion into two part; cell proliferative and non-proliferative mechanisms. To quantify the tissue growth, we will measure luminal sizes of the tracheal tubes and the cell proliferation rates at different developmental time points. Changing epithelial cell shapes and alignment will be examined by three-dimensional imaging with single cell-resolution and quantitatively analyzed on PC.

Developmental processes of large luminal tubular tissues are poorly understood although a failure of normal luminal developmental causes strictures of the inner organs. Our research would clarify how an alignment of epithelial cells and single cell morphology contribute the luminal expansion of the tracheal tube in addition to the increase in epithelial cell population. These new knowledge might give us a new insight of understanding congenital disorders with strictures in the inner organs.