TY - JOUR
T1 - Global shape of Toll activation is determined by wntD enhancer properties
AU - Rahimi, Neta
AU - Carmon, Shari
AU - Averbukh, Inna
AU - Khajouei, Farzaneh
AU - Sinha, Saurabh
AU - Schejter, Eyal D.
AU - Barkai, Naama
AU - Shilo, Ben-Zion
N1 - We thank S. Ben-Moshe, K. Bahar Halpern, and S. Itzkovitz for advice on smFISH and Y. Addadi and O. Golani for help in acquisition and analysis of light sheet fluorescence microscopy images. Imaging using the light sheet fluorescence microscope was made possible thanks to the de Picciotto-Lesser Cell Observatory founded in memory of Wolf and Ruth Lesser. We thank members of the B.-Z.S. and N.B. laboratories for fruitful discussions. This work was supported in part by NIH Grants R01 GM114341 and R35 GM131819 (to S.S.); United States-Israel Binational Science Foundation Grant 2017055 (to N.B.); United States-Israel Binational Science Foundation Grant 2015063 (to E.D.S. and B.-Z.S.); and a research grant from the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics (to B.-Z.S.). N.B. is the incumbent of the Lorna Greenberg Scherzer Professorial Chair, and B.-Z.S. is the incumbent of the Hilda and Cecil Lewis Professorial Chair in Molecular Genetics. Author contributions: N.R., S.C., I.A., E.D.S., N.B., and B.-Z.S. designed research; N.R. and S.C. performed research; S.C., I.A., F.K., and S.S. contributed new reagents/analytic tools; N.R., I.A., F.K., S.S., E.D.S., N.B., and B.-Z.S. analyzed data; and E.D.S., N.B., and B.-Z.S. wrote the paper.
PY - 2020/1/21
Y1 - 2020/1/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85078190748&partnerID=8YFLogxK
U2 - 10.1073/pnas.1918268117
DO - 10.1073/pnas.1918268117
M3 - مقالة
SN - 0027-8424
VL - 117
SP - 1552
EP - 1558
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -