EARLY DEVELOPMENT OF LUNG

University Of Washington, Seattle WA

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Abstract

Although the development and growth of the mammalian lung is one of the most studied and well documented of all the organs of the body little is known of the actual mechanisms which control and affect its early development. We have started developing model mechanisms for generating the initial branching that takes place in the early development of the lung to try to obtain some understanding of the underlying developmental processes involved. We have constructed a preliminary mathematical model which may describe the formation and development of the lung during the pseudoglandular stages of development. This preliminary model takes into account available experimental evidence and may provide a possible mechanism which describes the dichotomous branching of the lung bud in the early stages. The main features of the model are mechanical factors, such as strain and pressure, which are known to have a major effect on lung cells and their proliferation rates. It is known from experimental results and from our preliminary numerical results that pressure in an inflating axisymmetric thin sheet (which we hypothesize for the limb membrane) gives rise to strain fields and curvature distributions which are maximal at certain regions of the membrane. We are currently investigating whether such fields arising in lung buds may provide the stimulus for mitosis leading to bifurcation in the regions where branching occurs. This work will be written up for publication.