Abstract
Buffering variability in morphogen distribution is essential for reproducible patterning. A theoretically proposed class of mechanisms, termed "distal pinning," achieves robustness by combining local sensing of morphogen levels with global modulation of gradient spread. Here, we demonstrate a critical role for morphogen sensing by a gene enhancer, which ultimately determines the final global distribution of the morphogen and enables reproducible patterning. Specifically, we show that, while the pattern of Toll activation in the early Drosophila embryo is robust to gene dosage of its locally produced regulator, WntD, it is sensitive to a single-nucleotide change in the wntD enhancer. Thus, enhancer properties of locally produced WntD directly impinge on the global morphogen profile.
Keywords:
Drosophila; Toll signaling; embryogenesis; integral feedback; morphogen gradients.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Binding Sites
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Body Patterning
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Drosophila / embryology*
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Drosophila / genetics*
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Drosophila / metabolism*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Embryonic Development / genetics
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Enhancer Elements, Genetic / genetics*
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Gastrula / physiology
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Gene Dosage
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Gene Expression Regulation, Developmental
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HMGB Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Morphogenesis / genetics
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Morphogenesis / physiology
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Repressor Proteins / metabolism
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Sequence Alignment
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Signal Transduction / genetics
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Signal Transduction / physiology
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Toll-Like Receptors / genetics
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Toll-Like Receptors / metabolism
Substances
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Drosophila Proteins
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HMGB Proteins
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Intracellular Signaling Peptides and Proteins
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Repressor Proteins
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Tl protein, Drosophila
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Toll-Like Receptors
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WntD protein, Drosophila
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cic protein, Drosophila