Abstract
During embryonic development, many organs form by extensive branching of epithelia through the formation of clefts and buds. In cleft formation, buds are delineated by the conversion of epithelial cell-cell adhesions to cell-matrix adhesions, but the mechanisms of cleft formation are not clear. We have identified Btbd7 as a dynamic regulator of branching morphogenesis. Btbd7 provides a mechanistic link between the extracellular matrix and cleft propagation through its highly focal expression leading to local regulation of Snail2 (Slug), E-cadherin, and epithelial cell motility. Inhibition experiments show that Btbd7 is required for branching of embryonic mammalian salivary glands and lungs. Hence, Btbd7 is a regulatory gene that promotes epithelial tissue remodeling and formation of branched organs.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Cadherins / metabolism
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Cell Adhesion
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Cell Line
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Cell Movement
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Dogs
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Epithelial Cells / physiology*
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Fibronectins / genetics
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Fibronectins / metabolism
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Genes, Regulator
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Lung / embryology*
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Lung / metabolism
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Mice
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Mice, Inbred ICR
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Models, Biological
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Molecular Sequence Data
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Morphogenesis*
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Nuclear Proteins
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Organ Culture Techniques
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Proteins / chemistry
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Proteins / genetics*
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Proteins / physiology*
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RNA, Small Interfering
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Salivary Glands / embryology*
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Salivary Glands / metabolism
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Snail Family Transcription Factors
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Submandibular Gland / embryology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Btbd7 protein, mouse
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Cadherins
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Fibronectins
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Nuclear Proteins
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Proteins
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RNA, Small Interfering
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Snai1 protein, mouse
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Snai2 protein, mouse
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Snail Family Transcription Factors
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Transcription Factors