title: Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape.
abstract: Changing the morphology of a simple epithelial tube to form a highly ramified branching network requires changes in cell behavior that lead to tissue-wide changes in organ shape. How epithelial cells in branched organs modulate their shape and behavior to promote bending and sculpting of the epithelial sheet is not well understood, and the mechanisms underlying this process remain obscure. We show that the Wnt receptor Frizzled 2 (Fzd2) is required for domain branch formation during the initial establishment of the respiratory tree. Live imaging and transcriptome analysis of lung-branching morphogenesis demonstrate that Fzd2 promotes changes in epithelial cell length and shape. These changes in cell morphology deform the developing epithelial tube to generate and maintain new domain branches. Fzd2 controls branch formation and the shape of the epithelial tube by regulating Rho signaling and by the localization of phospho-myosin light chain 2, in turn controlling the changes in the shape of epithelial cells during morphogenesis. This study demonstrates the importance of Wnt/Fzd2 signaling in promoting and maintaining changes in epithelial cell shape that affect development of a branching network.
authors.affiliation: Departments of Cell and Developmental Biology and.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Kadzik
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Rochester, Rochester, NY 14642.
authors.forename: Ethan David
authors.initials: ED
authors.lastname: Cohen
authors.affiliation: Medicine.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Morley
authors.affiliation: Medicine, Cardiovascular Institute, and.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Stewart
authors.affiliation: Medicine.
authors.forename: Min Min
authors.initials: MM
authors.lastname: Lu
authors.affiliation: Departments of Cell and Developmental Biology and Medicine, Cardiovascular Institute, and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104; and emorrise@mail.med.upenn.edu.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
mesh_terms: D000818:Animals; D048430:Cell Shape; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D051157:Frizzled Receptors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D011247:Pregnancy; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: C495267:CTNNB1 protein, mouse; D051157:Frizzled Receptors; C489743:Fzd2 protein, mouse; D053823:Hedgehog Proteins; D008024:Ligands; C465570:Shh protein, mouse; D051176:beta Catenin; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
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