Peripheral Innervation and Pattern Formation During Lung Development

Abstract

It has recently been shown that peripheral innervation maintains epithelial progenitor cells in an undifferentiated state, which is a necessary condition for epithelial morphogenesis in the mouse salivary gland. However, it remains unclear whether neural development affects the morphogenesis of additional branching organs. As similar progenitor cells exist and are innervated in the lungs, this thesis examines how the peripheral nervous system affects lung morphogenesis, using chick embryos as a model system. The initial mapping of the nerves, blood vessels, and epithelium across days four through seven of development revealed that although they may share common molecular cues, there is not a strongly definitive relationship between the three branching patterns. To determine if innervation is required for lung morphogenesis, explants were cultured in the presence of BW 284C51, an acetylcholinesterase inhibitor that has been shown to reduce nerve growth in culture. The results of these experiments suggest that a reduction or absence of pulmonary nerves leads to more extensive epithelial growth. Furthermore, evidence supported the conclusion that while peripheral innervation does affect lung morphogenesis, it may not be necessary for its occurrence. Research that seeks to contribute to a greater understanding of how the peripheral nervous system affects lung development is important to the medical field. Such endeavors can contribute to the discovery of new treatments surrounding developmental lung problems and to techniques in regenerative medicine.