Global shape of Toll activation is determined by wntD enhancer properties

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 critic...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-01, Vol.117 (3), p.1552-1558
Main Authors: Rahimia, Neta, Carmona, Shari, Averbukha, Inna, Khajouei, Farzaneh, Sinha, Saurabh, Schejter, Eyal D., Barkai, Naama, Shilo, Ben-Zion
Format: Article
Language:English
Subjects:
Activation
Animals
Binding Sites
Biological Sciences
Body Patterning
Drosophila - embryology
Drosophila - genetics
Drosophila - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Embryonic Development - genetics
Embryos
Enhancer Elements, Genetic - genetics
Fruit flies
Gastrula - physiology
Gene Dosage
Gene Expression Regulation, Developmental
HMGB Proteins - metabolism
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Morphogenesis - genetics
Morphogenesis - physiology
Nucleotides
Patterning
Repressor Proteins - metabolism
Sequence Alignment
Signal Transduction - genetics
Signal Transduction - physiology
Toll-Like Receptors - genetics
Toll-Like Receptors - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1918268117