Protein Patterning in Embryogenesis

Many biological processes, including development, depend on the formation of patterned distributions of specific proteins within cells. One paradigmatic example of this kind of cell polarization is the first cell division during embryogenesis in the nematode worm C. elegans. In a study published this week in Nature Communications,LMU scientists identified two crucial mechanisms that contribute to the robust orientation of the polarized pattern of the PAR (partitioning defective) proteins along the long axis of the fertilized egg.

The first cell division of the elongated C. elegans egg is asymmetric, and it determines the future front and back sides of the worm. This anterior–posterior polarity of the embryo is also defined by PAR proteins, which can be divided into two subgroups: aPARs and pPARs, which bind to the anterior and posterior membrane, respectively.

In the unfertilized egg, all PAR proteins diffuse freely and are evenly distributed throughout the cell. In principle, all of them could bind to the membrane at any point. But due to a mutual antagonism between aPARs and pPARs, each group of proteins soon builds a domain on the membrane that excludes the other group.

“We use mathematical models and numerical simulations to explore the mechanisms that underlie the formation of protein patterns in cells,” says first author Raphaela Gessele. “In this study, we analyzed what determines the orientation of the aPAR–pPAR pattern; specifically, what aligns the polarized pattern with the long axis of the egg.”

Each group of PARs can bind to the membrane and antagonistically remove the other protein group from the membrane by phosphorylation. Simulations showed that the dynamics of cycling between the phosphorylated and dephosphorylated states of the aPARs and pPARs are a critical factor in the process of axis selection at patterning onset.

The study shows that the ellipsoidal geometry of the fertilized egg also influences the patterning process. Owing to the difference in curvature, recently detached and freely diffusing proteins are more likely to reencounter the membrane at the poles than elsewhere in the cell.

“Antagonistic proteins exclude each other proportional to their membrane concentration, which stabilizes domains,” Gessele explains. “Depending on the respective lifetimes of the phosphorylated forms, the protein domains localize in the midcell region or at the cell poles at first; however, the final polarization in the three-dimensional embryo is always aligned with the long axis.”