Mechanism and implications of morphogen shuttling: Lessons learned from dorsal and Cactus in Drosophila

• Published in: Developmental biology Vol. 461; no. 1; pp. 13 - 18
• Main Authors: Schloop, Allison E., Carrell-Noel, Sophia, Friedman, Jeramey, Thomas, Alexander, Reeves, Gregory T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2020
• Subjects: Animals; Body Patterning - genetics; Body Patterning - physiology; Cactus; Development; Diffusion; DNA-Binding Proteins - metabolism; Dorsal; Dorsal-ventral axis; Drosophila melanogaster - embryology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Embryo; Embryo, Nonmammalian - embryology; Embryonic Development - physiology; I-kappa B Proteins - antagonists & inhibitors; Morphogen; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Shuttling; Toll; Transcription Factors - genetics; Transcription Factors - metabolism; Embryo; Morphogen; Cactus; Dorsal-ventral axis; Development; Dorsal; Toll; Shuttling; Diffusion
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2020.01.011

In a developing animal, morphogen gradients act to pattern tissues into distinct domains of cell types. However, despite their prevalence in development, morphogen gradient formation is a matter of debate. In our recent publication, we showed that the Dorsal/NF-κB morphogen gradient, which patterns the DV axis of the early Drosophila embryo, is partially established by a mechanism of facilitated diffusion. This mechanism, also known as “shuttling,” occurs when a binding partner of the morphogen facilitates the diffusion of the morphogen, allowing it to accumulate at a given site. In this case, the inhibitor Cactus/IκB facilitates the diffusion of Dorsal/NF-κB. In the fly embryo, we used computation and experiment to not only show that shuttling occurs in the embryo, but also that it enables the viability of embryos that inherit only one copy of dorsal maternally. In this commentary, we further discuss our evidence behind the shuttling mechanism, the previous literature data explained by the mechanism, and how it may also be critical for robustness of development. Finally, we briefly provide additional experimental data pointing toward an interaction between Dorsal and BMP signaling that is likely affected by shuttling. •Dorsal gradient formation is aided by facilitated diffusion, or shuttling by Cactus.•The shuttling mechanism requires four processes to be in balance.•Shuttling and saturation of Toll signaling explains Dorsal gradient robustness.•Shuttling mediates diverse processes, including scaling and signaling crosstalk.