Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland Journal Article
| Authors: | Dean, C. H.; Miller, L. A. D.; Smith, A. N.; Dufort, D.; Lang, R. A.; Niswander, L. A. |
| Article Title: | Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland |
| Abstract: | 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. © 2005 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; gene mutation; nonhuman; protein function; cell proliferation; mouse; animals; mice; mice, knockout; animal tissue; cell structure; models, biological; bone morphogenetic protein; transforming growth factor beta; embryo; culture medium; protein stability; dna, antisense; morphogenesis; mice, transgenic; gene expression regulation, developmental; gene repression; lung; base sequence; gene control; branching morphogenesis; up-regulation; wnt proteins; beta catenin; wnt protein; comprehension; dna, complementary; bone morphogenetic proteins; modulation; adherens junctions; wnt signaling; β-catenin; conditioning; fibroblast growth factor 10; canonical analysis; lithium chloride; lung alveolus epithelium; lung development; lacrimal gland; lacrimal apparatus; morpholino |
| Journal Title: | Developmental Biology |
| Volume: | 286 |
| Issue: | 1 |
| ISSN: | 0012-1606 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2005-10-01 |
| Start Page: | 270 |
| End Page: | 286 |
| Language: | English |
| DOI: | 10.1016/j.ydbio.2005.07.034 |
| PUBMED: | 16126193 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 49" - "Export Date: 24 October 2012" - "CODEN: DEBIA" - "Source: Scopus" |
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