More GPR-1/2 (red) at the posterior end (right) of the embryo leads to asymmetric cell division.


Polarity is set early on—even single cell stage embryos already know their front from back. Recent research by the laboratory of Pierre Gönczy (Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland) is identifying how this polarity is translated into differences in cell behavior.

Polarity in worm embryos, which is set by the PAR proteins, produces an unequal first mitotic division, and thus a small posterior and large anterior blastomere. A previous screen by Gönczy identified two proteins, GPR-1 and GPR-2, necessary for this unequal division. Although direct interactions between PARs and GPR-1/2 have not been demonstrated, Kelly Colombo, Gönczy, and colleagues now demonstrate an asymmetric GPR-1/2 distribution that depends on PAR proteins. Higher levels of GPR-1/2 in the posterior are proposed to activate two Gα subunits. The group used RNAi and spindle severing experiments to show that these two Gα's and GPR-1/2 are required for asymmetric spindle elongation, in which the posterior spindle pole moves further and more quickly than the anterior pole, thus placing the division plane closer to the posterior end.

The resulting larger anterior blastomere divides about two minutes before its posterior counterpart. In a second paper Gönczy, Michael Brauchle, and Karine Baumer show that this time lag is due in part to differential activation of a DNA replication checkpoint.

Inactivation of checkpoint proteins such as ATL-1 decreased the mitotic lag between blastomeres to about 75 s. “Usually checkpoints are used to take care of DNA replication problems. But in this case, it's used for developmental purposes,” says Gönczy. The sizes of the blastomeres may account for the difference in checkpoint activation. When the group equalized the blastomere sizes by inactivating GPR-1/2, they again decreased the time difference to 75 s. With less cytoplasm, the posterior blastomere may be allocated fewer molecules of a limiting replication factor, and would thus have difficulties completing S phase, thus triggering the checkpoint. ▪


Colombo, K., et al. 2003. Science. 10.1126/science.1084146.

Brauchle, A., et al. 2003. Curr. Biol. 13:308–314.