title: Wnt2 signaling is necessary and sufficient to activate the airway smooth muscle program in the lung by regulating myocardin/Mrtf-B and Fgf10 expression.
abstract: Smooth muscle in the lung is thought to derive from the developing lung mesenchyme. Smooth muscle formation relies upon coordination of both autocrine and paracrine signaling between the budding epithelium and adjacent mesenchyme to govern its proliferation and differentiation. However, the pathways initiating the earliest aspects of smooth muscle specification and differentiation in the lung are poorly understood. Here, we identify the Wnt2 ligand as a critical regulator of the earliest aspects of lung airway smooth muscle development. Using Wnt2 loss and gain of function models, we show that Wnt2 signaling is necessary and sufficient for activation of a transcriptional and signaling network critical for smooth muscle specification and differentiation including myocardin/Mrtf-B and the signaling factor Fgf10. These studies place Wnt2 high in a hierarchy of signaling molecules that promote the earliest aspects of lung airway smooth muscle development.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Goss
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Lan
authors.initials: L
authors.lastname: Cheng
authors.forename: Jifu
authors.initials: J
authors.lastname: Yang
authors.forename: Diane
authors.initials: D
authors.lastname: Zhou
authors.forename: Ethan David
authors.initials: ED
authors.lastname: Cohen
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D009130:Muscle, Smooth / Q000196:embryology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D051154:Wnt2 Protein / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D014157:Transcription Factors; D051154:Wnt2 Protein; D051176:beta Catenin; C503315:myocardin-related transcription factor B, mouse; D017479:Receptors, Platelet-Derived Growth Factor