Links between signal transduction, transcription and adhesion in epithelial bud development

• Published in: Nature (London) Vol. 422; no. 6929; pp. 317 - 322
• Main Authors: Fuchs, Elaine, Jamora, Colin, DasGupta, Ramanuj, Kocieniewski, Pawel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 20-03-2003; Nature Publishing Group
• Subjects: Adherens Junctions - metabolism; Adhesion; Animals; beta Catenin; Biological and medical sciences; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Cadherins - genetics; Cadherins - metabolism; Carrier Proteins; Cell Adhesion; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cellular biology; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - metabolism; Down-Regulation; Drosophila; Epithelial Cells - cytology; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Regulation, Developmental; Hair Follicle - cytology; Hair Follicle - embryology; Hair Follicle - metabolism; In Situ Hybridization; Lymphoid Enhancer-Binding Factor 1; Macromolecular Substances; Mice; Mice, Knockout; Mice, Transgenic; Molecular and cellular biology; Morphogenesis; Proteins; Proteins - genetics; Proteins - metabolism; Proto-Oncogene Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Teeth; Trans-Activators - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Wnt Proteins; Zebrafish Proteins; Stem cell; Cadherin; Gene expression; Adhesion; Morphogenesis; Signal transduction; Bone morphogenetic protein; Development; Epithelial cell; Polarity; Transcription factor; Catenin; Organ
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01458

The morphogenesis of organs as diverse as lungs, teeth and hair follicles is initiated by a downgrowth from a layer of epithelial stem cells. During follicular morphogenesis, stem cells form this bud structure by changing their polarity and cell-cell contacts. Here we show that this process is achieved through simultaneous receipt of two external signals: a Wnt protein to stabilize β-catenin, and a bone morphogenetic protein (BMP) inhibitor to produce Lef1. β-Catenin then binds to, and activates, Lef1 transcription complexes that appear to act uncharacteristically by downregulating the gene encoding E-cadherin, an important component of polarity and intercellular adhesion. When either signal is missing, functional Lef1 complexes are not made, and E-cadherin downregulation and follicle morphogenesis are impaired. In Drosophila, E-cadherin can influence the plane of cell division and cytoskeletal dynamics. Consistent with this notion, we show that forced elevation of E-cadherin levels block invagination and follicle production. Our findings reveal an intricate molecular programme that links two extracellular signalling pathways to the formation of a nuclear transcription factor that acts on target genes to remodel cellular junctions and permit follicle formation.