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

Matthew R Jones; Lei Chong; Saverio Bellusci

doi:10.3389/fcell.2020.620667

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

Front Cell Dev Biol. 2021 Jan 12:8:620667. doi: 10.3389/fcell.2020.620667. eCollection 2020.

Authors

Matthew R Jones^{1

2}, Lei Chong³, Saverio Bellusci^{1

2}

Affiliations

¹ Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Cardio-Pulmonary Institute and Department of Pulmonary and Critical Care Medicine and Infectious Diseases, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, Giessen, Germany.
³ National Key Clinical Specialty of Pediatric Respiratory Medicine, Discipline of Pediatric Respiratory Medicine, Institute of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

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) signaling 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 signaling. 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 remodeling 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 emphasize the known or speculative effects of Fgfr2b signaling 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.

Keywords: Fgf10; Fgfr2b; branching morphogenesis; epithelial-mesenchymal cross-talk; lung.

Publication types

Review