Global shape of Toll activation is determined by wntD enhancer properties

• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1918268117

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.