Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland
| Autor: | Richard A. Lang, April N. Smith, Lee Niswander, Charlotte H. Dean, Daniel Dufort, Leigh-Anne D. Miller |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
DNA Complementary animal structures Morpholino Bone Morphogenetic Protein 7 Lacrimal gland Mice Transgenic Biology Fibroblast growth factor Models Biological DNA Antisense Mice Transforming Growth Factor beta Internal medicine Morphogenesis medicine Branching morphogenesis Animals Lung Molecular Biology beta Catenin Cell Proliferation Mice Knockout FGF10 Base Sequence Lacrimal Apparatus Wnt signaling pathway Gene Expression Regulation Developmental LRP6 LRP5 Adherens Junctions Cell Biology β-catenin Wnt signaling Up-Regulation Cell biology Wnt Proteins medicine.anatomical_structure Endocrinology Bone Morphogenetic Proteins Lung development Fibroblast Growth Factor 10 WNT3A Signal Transduction Developmental Biology |
| Zdroj: | Developmental Biology. (1):270-286 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2005.07.034 |
| Popis: | Key gene families such as FGFs and BMPs are important mediators of branching morphogenesis. To understand whether Wnt genes, and in particular, the canonical Wnt signaling pathway also function in the branching process, we have used a combination of experimental and genetic gain and loss of function approaches to perturb the levels of canonical Wnt signaling in two arborized structures, the lung and the lacrimal gland. Here, we show that the addition of Wnt3a conditioned medium or LiCl strongly represses growth and proliferation of the lung and lacrimal gland, a result that was confirmed in vivo using a dominant stable mutation of β-catenin conditionally expressed in the lacrimal gland epithelium. In agreement with these data, knockdown of Wnt signaling with β-catenin morpholinos results in a greater number of branches and increased cell proliferation. In addition, we show that canonical Wnt signaling is able to modulate the levels of Fgf10 and suppress BMP-induced proliferation in the lacrimal gland. Thus, canonical Wnt signaling negatively regulates branching morphogenesis providing a balance to FGFs and BMPs which positively regulate this process. This multilayered control of growth and proliferation ensures that branched structures attain the morphology required to function efficiently. |
| Databáze: | OpenAIRE |
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