Fgf10/Fgfr2b Signaling Orchestrates the Symphony of Molecular, Cellular, and Physical Processes Required for Harmonious Airway Branching Morphogenesis

摘要

Airway branching morphogenesis depends on the intricate orchestration of numerous biological and physical factors connected across different spatial scales. One of the key regulatory pathways controlling airway branching is fibroblast growth factor 10 (Fgf10) signalling via its epithelial fibroblast growth factor receptor 2b (Fgfr2b). Fine reviews have been published on the molecular mechanisms, in general, involved in branching morphogenesis, including those mechanisms, in particular, connected to Fgf10/Fgfr2b signalling. However, a comprehensive review looking at all the major biological and physical factors involved in branching, at the different scales at which branching operates, and the known role of Fgf10/Fgfr2b therein, is missing. In the current review, we attempt to summarize the existing literature on airway branching morphogenesis by taking a broad approach. We focus on the biophysical and mechanical forces directly shaping epithelial bud initiation, branch elongation, and branch tip bifurcation. We then shift focus to more passive means by which branching proceeds, via extracellular matrix remodelling and the influence of the other pulmonary arborized networks: the vasculature and nerves. We end the review by briefly discussing work in computational modeling of airway branching. Throughout, we emphasise the known or speculative effects of Fgfr2b signalling at each point of discussion. It is our aim to promote an understanding of branching morphogenesis that captures the multi-scalar biological and physical nature of the phenomenon, and the interdisciplinary approach to its study.