Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis

Abstract

Embryogenesis relies on instructions provided by spatially organized signaling molecules known as morphogens. Understanding the principles behind morphogen distribution and how cells interpret locally this information remains a major challenge in developmental biology. Here, we introduce morphogen‐age measurements as a novel approach to test models of morphogen gradient formation. Using a tandem fluorescent timer as a protein age sensor, we find a gradient of increasing age of Bicoid along the anterior–posterior axis in the early Drosophila embryo. Quantitative analysis of the protein age distribution across the embryo reveals that the synthesis–diffusion–degradation model is the most likely model underlying Bicoid gradient formation, and rules out other hypotheses for gradient formation. Moreover, we show that the timer can detect transitions in the dynamics associated with syncytial cellularization. Our results provide new insight into Bicoid gradient formation and demonstrate how morphogen‐age information can complement knowledge about movement, abundance, and distribution, which should be widely applicable to other systems.

Patterning the Drosophila embryo: A paradigm for RNA‐based developmental genetic regulation

“…Because measuring these parameters in living embryos is technically very challenging, there have been inconsistent results among the different groups that investigate this question. However, a recent paper that used a tandem fluorescent protein timer to measure the age of Bcd protein at different positions along the anterior-posterior axis of the embryo improved upon earlier technologies and supports the original protein diffusion based model (Durrieu et al, 2018). To create such a timer, Bcd was tagged with two different fluorophores, a green one that matures quickly, and a red one that matures slowly.…”

The dynamic transmission of positional information in stau- mutants during Drosophila embryogenesis

“…We expect that studying the combination of the two mechanisms could be the key to revealing the mechanism of precise and robust pattern formation via dynamic transmission of positional information. Our newly developed measurement methods, together with recent developed dynamic measurement ( Bothma et al, 2018 ; Dubuis et al, 2013 ; Durrieu et al, 2018 ; Garcia et al, 2013 ; Huang et al, 2017 ; Lucas et al, 2013 ) and modeling ( Verd et al, 2017 ) tools, will facilitate the characterization of the dynamic transmission of positional information.…”

Quantifying temperature compensation of Bicoid gradients with a fast T-tunable microfluidic device

“…These predictions could help to design temperature-dependent dynamic measurements on these parameters, which could facilitate refining the extended SDD model to explore the temperature compensation of Bcd gradients in future studies. (20,29,43,44) and modeling (45), it also suggests it is very important to investigate the dynamics of the Bd system in its formation and interpretation.…”