Miller, Mayumi

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WNT2 and WNT7B Cooperative Signaling in Lung Development
(2012-01-01) Miller, Mayumi
The development of a complex organ, such as the lung, relies upon precisely controlled temporal and spatial expression patterns of signaling pathways for proper specification and differentiation of the cell types required to build a lung. While progress has been made in dissecting the network of signaling pathways and the integration of their positive and negative feedback mechanisms, there is still much to discover. For example, the Wnt signaling pathway is required for lung specification and growth, but a combinatorial role for Wnt ligands has not been investigated. In this dissertation, I combine mouse genetic models and in vitro and ex vivo lung culture assays, to determine a cooperative role for Wnt2 and Wnt7b in the developing lung. This body of work reveals the requirement of cooperative signaling between Wnt2 and Wnt7b for smooth muscle development and proximal to distal patterning of the lung. Additional findings reveal a role for the Pdgf pathway and homeobox genes in potentiating this cooperation. In total, these findings elucidate how strong bursts of Wnt signaling activity are spatially and temporally controlled to affect specific cell populations of the developing lung.