期刊
NATURE
卷 422, 期 6929, 页码 317-322出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature01458
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资金
- NIAMS NIH HHS [R01 AR031737-24, R01 AR031737] Funding Source: Medline
The morphogenesis of organs as diverse as lungs, teeth and hair follicles is initiated by a downgrowth from a layer of epithelial stem cells(1,2). 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 Writ protein to stabilize beta-catenin, and a bone morphogenetic protein (BMP) inhibitor to produce Lef1. beta-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(3). 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.
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