Lung Development

Team Leader
Mitsuru Morimoto (Ph.D.)

The organs of the body all play critical functional roles, which are made possible by the arrangement of differentiated cells into the structures specific to that organ. Such structures are formed throughout development, with the late embryonic and immediate postnatal periods being particularly important for the functional maturation of organ systems. Defects that arise during these organogenetic processes are closely linked to a wide range of diseases, while after birth, the body is constantly exposed to potentially damaging environmental stresses. The adult body does manifest a certain degree of regenerative ability, although this is by no means complete. To study organ formation, repair and regeneration, we have focused our research on the respiratory system in mouse.

Respiratory organs in higher mammals are characterized by their efficient gas exchange, enabled by the functions of specialized cells. The development of such organs relies on the coordinated activities of both epithelial and mesenchymal tissue types, which arise from tissue-specific populations of stem cells in the developing embryo. The epithelial tissues of the conducting airways serve as the channel for the intake and exhalation of gases in the respiratory cycle, and are composed mainly of Club, ciliated, and neuroendocrine cells. In our work to date, we have shown how these various cells interact and exchange information to maintain the appropriate balance in their respective cell numbers and distributions.

Despite its location in the body’s interior, the respiratory tract is constantly exposed to environmental factors, such as infections by viruses and bacteria, smoke, and chemical toxins that may damage the airway epithelium. This damage is rapidly repaired by regenerating epithelial cells supplied by somatic stem cells in the adult tissue, and as in development, the numbers and distribution of cells in the epithelium must be maintained at levels appropriate to each region of the airway.

We focus on issues of how tissue morphology influences the formation of stem cell/niche tissue complexes in the development, repair and regeneration of respiratory organs, as well as mechanisms regulating cell proliferation and differentiation in developmental and regenerative processes.

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Distribution of Club (green), neuroendocrine (red) and SPNC (blue) cells
Three dimensional image of embryonic bronchi reconstructed from multi-photon images
Spatial distinction of epithelial cell pattern on the conducting airway
Plastic cast of airway.
3D computer reconstruction of branching bronchiole
Position of neuroendocrine cells within the entire geometric architecture of the airways.