The transcription factor NF-κB plays an important role in the immune system, apoptosis, and inflammation. Dorsal, a Drosophila homolog of NF-κB, patterns the dorsal-ventral axis in the blastoderm embryo. During this stage, Dorsal is sequestered outside the nucleus by the IκB homolog Cactus. Toll signaling on the ventral side breaks the Dorsal/Cactus complex, allowing Dorsal to enter the nucleus to regulate target genes. Fluorescent data show that Dorsal accumulates on the ventral side of the syncytial blastoderm. Here we use both modeling and experiment to show that this accumulation is due to facilitated diffusion, or shuttling, of Dorsal/Cactus complex. We also show that active Toll receptors are limiting in wildtype embryos, which is a key factor in explaining global Dorsal gradient formation. Our results suggest that shuttling is necessary for viability of embryos from mothers with compromised dorsal levels. Therefore, Cactus not only has the primary role of regulating Dorsal nuclear import, but also a secondary role in shuttling. Given that this mechanism has been found in other, independent systems, we suggest it may be more prevalent than previously thought.
A facilitated diffusion mechanism establishes the Drosophila Dorsal gradient
These authors contributed equally to the work.
Currently Viewing Accepted Manuscript - Newer Version Available
Sophia N. Carrell, Michael D. O'Connell, Thomas Jacobsen, Amy E. Allen, Stephanie M. Smith, Gregory T. Reeves; A facilitated diffusion mechanism establishes the Drosophila Dorsal gradient. Development 2017; dev.155549. doi: https://doi.org/10.1242/dev.155549
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