A WntD-Dependent Integral Feedback Loop Attenuates Variability in Drosophila Toll Signaling

Developmental Cell
Neta RahimiBen-Zion Shilo

Abstract

Patterning by morphogen gradients relies on the capacity to generate reproducible distribution profiles. Morphogen spread depends on kinetic parameters, including diffusion and degradation rates, which vary between embryos, raising the question of how variability is controlled. We examined this in the context of Toll-dependent dorsoventral (DV) patterning of the Drosophila embryo. We find that low embryo-to-embryo variability in DV patterning relies on wntD, a Toll-target gene expressed initially at the posterior pole. WntD protein is secreted and disperses in the extracellular milieu, associates with its receptor Frizzled4, and inhibits the Toll pathway by blocking the Toll extracellular domain. Mathematical modeling predicts that WntD accumulates until the Toll gradient narrows to its desired spread, and we support this feedback experimentally. This circuit exemplifies a broadly applicable induction-contraction mechanism, which reduces patterning variability through a restricted morphogen-dependent expression of a secreted diffusible inhibitor.

References

Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·K Isoda, C Nüsslein-Volhard
Dec 5, 2003·Current Biology : CB·Petros LigoxygakisJean-Marc Reichhart
Nov 8, 2005·Current Biology : CB·Bernard Moussian, Siegfried Roth
Aug 19, 2006·Nature Reviews. Immunology·Nicholas J GayAlexander N R Weber
Apr 24, 2008·The Journal of Biological Chemistry·Wendy ChingRoel Nusse
Dec 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jitendra S KanodiaStanislav Y Shvartsman
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Louisa M LibermanAngelike Stathopoulos
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Naama Barkai, Ben-Zion Shilo
Apr 2, 2010·Proceedings of the National Academy of Sciences of the United States of America·Danny Ben-Zvi, Naama Barkai
Jun 15, 2011·Developmental Cell·Yoosik KimStanislav Y Shvartsman
Aug 2, 2011·Annual Review of Cell and Developmental Biology·Katherine W Rogers, Alexander F Schier
Nov 24, 2011·Developmental Biology·Patrick Herr, Konrad Basler
Jul 14, 2012·Development·Aharon HelmanZe'ev Paroush
Sep 7, 2012·Cold Spring Harbor Perspectives in Biology·Karl Willert, Roel Nusse
Feb 2, 2013·Trends in Genetics : TIG·Ben-Zion ShiloNaama Barkai
May 28, 2013·Cell·Mounia LaghaMichael S Levine
Aug 21, 2013·Differentiation; Research in Biological Diversity·Yulia ShwartzElazar Zelzer
Nov 5, 2013·Current Biology : CB·Jackie Gavin-SmythEdwin L Ferguson
May 27, 2014·Current Biology : CB·Mariela D PetkovaThomas Gregor
Aug 16, 2014·Wiley Interdisciplinary Reviews. Developmental Biology·David S Stein, Leslie M Stevens

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Citations

Jun 18, 2016·Fly·Olivier LamiableJean-Luc Imler
Nov 4, 2017·Development·Sophia N CarrellGregory T Reeves
Sep 1, 2017·Journal of the Royal Society, Interface·Javier Buceta
Jan 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Neta RahimiBen-Zion Shilo
Dec 22, 2019·Development·Daniel Čapek, Patrick Müller
Feb 13, 2019·Developmental Cell·Heath E Johnson, Jared E Toettcher
Jun 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Sarah McFannStanislav Y Shvartsman
Jun 1, 2021·Interface Focus·Johannes Jaeger, Nick Monk
Dec 18, 2021·Development·Shari CarmonBen-Zion Shilo

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