Asymmetry in the embryo starts with the first cell division. Daniels et al. show that one protein's asymmetrical distribution at this division is maintained by differential diffusion behavior.
In worms, PIE-1 is a germline-determining factor that represses somatic cell transcription programs. It starts off distributed symmetrically in the egg, but after fertilization it must be divvied up with each division. So what keeps PIE-1 enriched on one side of the cell?
Daniels et al. ruled out immobilization and compartmentalization of the protein by analyzing the mobility of fluorescent PIE-1. They also showed that although localization of PIE-1 requires the reciprocal localization of a suspected PIE-1 degrader called MEX-5/6, this protein in fact does not degrade PIE-1 in the zygote.
Instead, PIE-1's asymmetry is down to diffusion kinetics. Analysis of single molecule movement revealed most PIE-1 molecules at the front of the cell moved quickly. At the rear, slow diffusers made up the majority and there was even a group of super-slow diffusers. Based on these findings, the team developed a model that explains PIE-1's distribution.
So what causes the difference in diffusion? The kinetics of the slowest group fits well with that of P granules, which are known to be enriched at the back of the cell and with which PIE-1 has been reported to interact. As for the slow diffusers, which account for the majority of the PIE-1 molecules at the rear, the authors suggest that PIE-1 is interacting with some type of RNA species. The next step is to determine whether this prediction is correct, and if so, what spatially restricts the RNA binding. RW