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Global shape of Toll activation is determined by wntD enhancer properties.

Neta RahimiShari CarmonInna AverbukhFarzaneh KhajoueiSaurabh SinhaEyal D SchejterNaama BarkaiBen-Zion Shilo
Published in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.
Keyphrases
  • transcription factor
  • binding protein
  • copy number
  • genome wide
  • minimally invasive
  • gene expression
  • pregnant women
  • pregnancy outcomes
  • genome wide analysis