Abstract
Morphogen gradients pattern tissues and organs during development. When morphogen production is spatially restricted, diffusion and degradation are sufficient to generate sharp concentration gradients. It is less clear how sharp gradients can arise within the source of a broadly expressed morphogen. A recent solution relies on localized production of an inhibitor outside the domain of morphogen production, which effectively redistributes (shuttles) and concentrates the morphogen within its expression domain. Here, we study how a sharp gradient is established without a localized inhibitor, focusing on early dorsoventral patterning of the Drosophila embryo, where an active ligand and its inhibitor are concomitantly generated in a broad ventral domain. Using theory and experiments, we show that a sharp Toll activation gradient is produced through "self-organized shuttling," which dynamically relocalizes inhibitor production to lateral regions, followed by inhibitor-dependent ventral shuttling of the activating ligand Spätzle. Shuttling may represent a general paradigm for patterning early embryos. PaperFlick:
| Original language | English |
|---|---|
| Pages (from-to) | 1016-1028 |
| Number of pages | 13 |
| Journal | Cell |
| Volume | 150 |
| Issue number | 5 |
| DOIs | |
| State | Published - 31 Aug 2012 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank R. DeLotto, T. Ip, Z. Paroush, and D. Stein for reagents; Y. Gilad, A. Rubinstein, and I. Koren for technical help; T. Volk for insightful suggestions; and Orit Bechar, Tali Wiesel, and Itzchak Reuven for their dedicated graphic design and animation work. We thank members of our groups for fruitful discussions. D.B.-Z. is supported by the Adams Fellowship Program of the Israeli Academy of Sciences and Humanities. This work was supported by the European Research Council, Israel Science Foundation, Minerva, and the Helen and Martin Kimmel Award for Innovative Investigations to N.B., who is the incumbent of the Lorna Greenberg Scherzer Professorial Chair, and the Minerva Foundation to B.-Z.S., who is an incumbent of the Hilda and Cecil Lewis Professorial Chair in Molecular Genetics.