Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis

DURRIEU, LUCÍA; KIRRMAIER, DANIEL; SCHNEIDT, TATJANA; KATS, ILIA; RAGAVAN, SARADA; HUFNAGEL, LARS; SAUNDERS, TIMOTHY; KNOP, MICHAEL

MOLECULAR SYSTEMS BIOLOGY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2018

1744-4292

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.